Etiological Factors and Symptom Triggers in Functional Motor Symptoms and Functional Seizures: A Pilot Investigation.

OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.

A neurostructural biomarker of dissociative amnesia: a hippocampal study in dissociative identity disorder.

BACKGROUND: Little is known about the neural correlates of dissociative amnesia, a transdiagnostic symptom mostly present in the dissociative disorders and core characteristic of dissociative identity disorder (DID). Given the vital role of the hippocampus in memory, a prime candidate for investigation is whether total and/or subfield hippocampal volume can serve as biological markers of dissociative amnesia. METHODS: A total of 75 women, 32 with DID and 43 matched healthy controls (HC), underwent structural magnetic resonance imaging (MRI). Using Freesurfer (version 6.0), volumes were extracted for bilateral global hippocampus, cornu ammonis (CA) 1-4, the granule cell molecular layer of the dentate gyrus (GC-ML-DG), fimbria, hippocampal-amygdaloid transition area (HATA), parasubiculum, presubiculum and subiculum. Analyses of covariance showed volumetric differences between DID and HC. Partial correlations exhibited relationships between the three factors of the dissociative experience scale scores (dissociative amnesia, absorption, depersonalisation/derealisation) and traumatisation measures with hippocampal global and subfield volumes. RESULTS: Hippocampal volumes were found to be smaller in DID as compared with HC in bilateral global hippocampus and bilateral CA1, right CA4, right GC-ML-DG, and left presubiculum. Dissociative amnesia was the only dissociative symptom that correlated uniquely and significantly with reduced bilateral hippocampal CA1 subfield volumes. Regarding traumatisation, only emotional neglect correlated negatively with bilateral global hippocampus, bilateral CA1, CA4 and GC-ML-DG, and right CA3. CONCLUSION: We propose decreased CA1 volume as a biomarker for dissociative amnesia. We also propose that traumatisation, specifically emotional neglect, is interlinked with dissociative amnesia in having a detrimental effect on hippocampal volume.

No Self Without Salience: Affective and Self-relevance Ratings of 552 Emotionally Valenced and Neutral Dutch Words.

It is unknown how self-relevance is dependent on emotional salience. Emotional salience encompasses an individual's degree of attraction or aversion to emotionally-valenced information. The current study investigated the interconnection between self and salience through the evaluation of emotional valence and self-relevance. 56 native Dutch participants completed a questionnaire assessing valence, intensity, and self-relevance of 552 Dutch nouns and verbs. One-way repeated-measures ANCOVA investigated the relationship between valence and self, age and gender. Repeated-measures ANCOVA also tested the relationship between valence and self with intensity ratings and effects of gender and age. Results showed a significant main effect of valence for self-relevant words. Intensity analyses showed a main effect of valence but not of self-relevance. There were no significant effects of gender and age. The most important finding presents that self-relevance is dependent on valence. These findings concerning the relationship between self and salience opens avenues to study an individual's self-definition.

Dissociative identity disorder: out of the shadows at last?

Dissociative identity disorder (DID) is a severely debilitating disorder. Despite recognition in the current and past versions of the DSM, DID remains a controversial psychiatric disorder, which hampers its diagnosis and treatment. Neurobiological evidence regarding the aetiology of DID supports clinical observations that it is a severe form of post-traumatic stress disorder.

Aiding the diagnosis of dissociative identity disorder: pattern recognition study of brain biomarkers.

BACKGROUND: A diagnosis of dissociative identity disorder (DID) is controversial and prone to under- and misdiagnosis. From the moment of seeking treatment for symptoms to the time of an accurate diagnosis of DID individuals received an average of four prior other diagnoses and spent 7 years, with reports of up to 12 years, in mental health services. AIM: To investigate whether data-driven pattern recognition methodologies applied to structural brain images can provide biomarkers to aid DID diagnosis. METHOD: Structural brain images of 75 participants were included: 32 female individuals with DID and 43 matched healthy controls. Individuals with DID were recruited from psychiatry and psychotherapy out-patient clinics. Probabilistic pattern classifiers were trained to discriminate cohorts based on measures of brain morphology. RESULTS: The pattern classifiers were able to accurately discriminate between individuals with DID and healthy controls with high sensitivity (72%) and specificity (74%) on the basis of brain structure. These findings provide evidence for a biological basis for distinguishing between DID-affected and healthy individuals. CONCLUSIONS: We propose a pattern of neuroimaging biomarkers that could be used to inform the identification of individuals with DID from healthy controls at the individual level. This is important and clinically relevant because the DID diagnosis is controversial and individuals with DID are often misdiagnosed. Ultimately, the application of pattern recognition methodologies could prevent unnecessary suffering of individuals with DID because of an earlier accurate diagnosis, which will facilitate faster and targeted interventions. DECLARATION OF INTEREST: The authors declare no competing financial interests.

Connectomic correlates of response to treatment in first-episode psychosis.

Connectomic approaches using diffusion tensor imaging have contributed to our understanding of brain changes in psychosis, and could provide further insights into the neural mechanisms underlying response to antipsychotic treatment. We here studied the brain network organization in patients at their first episode of psychosis, evaluating whether connectome-based descriptions of brain networks predict response to treatment, and whether they change after treatment. Seventy-six patients with a first episode of psychosis and 74 healthy controls were included. Thirty-three patients were classified as responders after 12 weeks of antipsychotic treatment. Baseline brain structural networks were built using whole-brain diffusion tensor imaging tractography, and analysed using graph analysis and network-based statistics to explore baseline characteristics of patients who subsequently responded to treatment. A subgroup of 43 patients was rescanned at the 12-week follow-up, to study connectomic changes over time in relation to treatment response. At baseline, those subjects who subsequently responded to treatment, compared to those that did not, showed higher global efficiency in their structural connectomes, a network configuration that theoretically facilitates the flow of information. We did not find specific connectomic changes related to treatment response after 12 weeks of treatment. Our data suggest that patients who have an efficiently-wired connectome at first onset of psychosis show a better subsequent response to antipsychotics. However, response is not accompanied by specific structural changes over time detectable with this method.

Volumetric grey matter alterations in adolescents and adults born very preterm suggest accelerated brain maturation.

Previous research investigating structural neurodevelopmental alterations in individuals who were born very preterm demonstrated a complex pattern of grey matter changes that defy straightforward summary. Here we addressed this problem by characterising volumetric brain alterations in individuals who were born very preterm from adolescence to adulthood at three hierarchically related levels - global, modular and regional. We demarcated structural components that were either particularly resilient or vulnerable to the impact of very preterm birth. We showed that individuals who were born very preterm had smaller global grey matter volume compared to controls, with subcortical and medial temporal regions being particularly affected. Conversely, frontal and lateral parieto-temporal cortices were relatively resilient to the effects of very preterm birth, possibly indicating compensatory mechanisms. Exploratory analyses supported this hypothesis by showing a stronger association between lateral parieto-temporal volume and IQ in the very preterm group compared to controls. We then related these alterations to brain maturation processes. Very preterm individuals exhibited a higher maturation index compared to controls, indicating accelerated brain maturation and this was specifically associated with younger gestational age. We discuss how the findings of accelerated maturation might be reconciled with evidence of delayed maturation at earlier stages of development.

Effects of aripiprazole and haloperidol on neural activation during a simple motor task in healthy individuals: A functional MRI study.

The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc.

The Psychobiology of Authentic and Simulated Dissociative Personality States: The Full Monty.

The etiology of dissociative identity disorder (DID) remains a topic of debate. Proponents of the fantasy model and the trauma model of DID have both called for more empirical research. To this end, the current study presents new and extended data analyses of a previously published H2O positron emission tomography imaging study. This study included 29 subjects: 11 patients with DID and 10 high- and 8 low-fantasy-prone DID-simulating mentally healthy control subjects. All subjects underwent an autobiographical memory script-driven (neutral and trauma related) imagery paradigm in 2 (simulated) dissociative personality states (neutral and trauma related). Psychobiological and psychophysiological data were obtained. Results of the new post-hoc tests on the psychophysiological responses support the trauma model. New results of the brain imaging data did not support the fantasy model. This study extends previously published results by offering important new supporting data for the trauma model of DID.

Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms.

Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared with HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared with HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders.

Inter-identity amnesia in dissociative identity disorder resolved: A behavioural and neurobiological study.

INTRODUCTION: Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between dissociative identity states. Studies have found conflicting results regarding memory transfer between dissociative identity states. Here, we investigated inter-identity amnesia in individuals with DID using self-relevant, subject specific stimuli, and behavioural and neural measures. METHODS: Data of 46 matched participants were included; 14 individuals with DID in a trauma-avoidant state, 16 trauma-avoiding DID simulators, and 16 healthy controls. Reaction times and neural activation patterns related to three types of subject specific words were acquired and statistically analysed, namely non-self-relevant trauma-related words (NSt), self-relevant trauma-related words from a trauma-avoidant identity state (St), and trauma-related words from a trauma-related identity state (XSt). RESULTS: We found no differences in reaction times between XSt and St words and faster reaction times for XSt over NSt. Reaction times of the diagnosed DID group were the longest. Increased brain activation to XSt words was found in the frontal and parietal regions, while decreased brain activity was found in the anterior cingulate cortex in the diagnosed DID group. DISCUSSION: The current study reproduces and amalgamates previous behavioural reports as well as brain activation patterns. Our finding of increased cognitive control over self-relevant trauma-related knowledge processing has important clinical implications and calls for the redefinition of "inter-identity amnesia" to "inter-identity avoidance".

Biomarkers of dissociation.

Dissociative symptoms present transdiagnostically and are related to poor clinical outcome. Research into the biological correlates of dissociation remains limited. This editorial summarises and discusses papers from this themed series of BJPsych Open that contribute to unravelling the biological correlates of dissociative symptomatology with the aim of improving treatment and treatment outcome.

Interoception in functional motor symptoms and functional seizures: Preliminary evidence of intact accuracy alongside reduced insight and altered sensibility.

Altered interoception may be a pathophysiological mechanism in functional neurological disorder (FND). However, findings have been inconsistent across interoceptive dimensions in FND including functional motor symptoms (FMS) and seizures (FS). Here, individuals with FMS/FS (n = 17) and healthy controls (HC, n = 17) completed measures of interoceptive accuracy and insight (adapted heartbeat tracking task [HTT] with confidence ratings), a time estimation control task (TET) and the Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) to assess interoceptive sensibility. The groups did not differ in interoceptive accuracy (p = 1.00, g = 0.00) or confidence (p = .99, g = 0.004), although the FMS/FS group displayed lower scores on the "Not-Distracting" (p < .001, g = 1.42) and "Trusting" (p = .005, g = 1.17) MAIA-2 subscales, relative to HCs. The groups did not differ in TET performance (p = .82, g = 0.08). There was a positive relationship between HTT accuracy and confidence (insight) in HCs (r = .61, p = .016) but not in FMS/FS (r = 0.11, p = .69). HTT confidence was positively correlated with MAIA-2 "Self-Regulation" (r = 0.77, p = .002) and negatively correlated with FND symptom severity (r = -0.84, p < .001) and impact (r = -0.86, p < .001) in FMS/FS. Impaired interoceptive accuracy may not be a core feature in FMS/FS, but reduced insight and altered sensibility may be relevant. Reduced certainty in self-evaluations of bodily experiences may contribute to the pathogenesis of FND symptoms.

Identity state-dependent self-relevance and emotional intensity ratings of words in dissociative identity disorder: A controlled longitudinal study.

INTRODUCTION: Dissociative identity disorder (DID) is characterized by, among others, amnesic episodes and the recurrence of different dissociative identity states. While consistently observed in clinical settings, to our knowledge, no controlled research study has shown the degree to which different identity states report autobiographical knowledge over time. Hence, the current study investigates self-relevance and emotional intensity ratings of words longitudinally. METHODS: Data of 46 participants were included: 13 individuals with DID, 11 DID-simulating actors, and a control group of 22 paired individuals. Individuals with DID and DID simulators participated once in the neutral identity state (NIS) and once in the trauma-related dissociative identity state (TIS). The control group paired 11 healthy controls with 11 participants with posttraumatic stress disorder (PTSD) as a NIS-TIS pair. Self-relevance ratings of different word types were collected in a baseline and a follow-up session, on average 6 weeks apart. A mixed ANOVA design was used to assess the effects of group, session, word type, and dissociative identity state. RESULTS: All participants in TIS and individuals with DID in NIS rated self-relevant trauma-related words more negatively. In the NIS, the control group rated self-relevant trauma-related words as less negative, whereas the ratings of simulating actors were intermediate. There was no group-dependent longitudinal effect for intensity ratings. CONCLUSIONS: This study was the first to confirm clinical observations that self-relevant and emotional processing are different between individuals with DID and controls, but consistent over time. Actors were unable to perfectly simulate DID. The finding that ratings of self-relevant trauma-related words differ between subgroups as included in the study is in line with clinical observations.

Objective and subjective neurocognitive functioning in functional motor symptoms and functional seizures: preliminary findings.

INTRODUCTION: This study aimed to provide a preliminary assessment of objective and subjective neurocognitive functioning in individuals with functional motor symptoms (FMS) and/or functional seizures (FS). We tested the hypotheses that the FMS/FS group would display poorer objective attentional and executive functioning, altered social cognition, and reduced metacognitive accuracy. METHOD: Individuals with FMS/FS (n = 16) and healthy controls (HCs, n = 17) completed an abbreviated CANTAB battery, and measures of intellectual functioning, subjective cognitive complaints, performance validity, and comorbid symptoms. Subjective performance ratings were obtained to assess local metacognitive accuracy. RESULTS: The groups were comparable in age (p = 0.45), sex (p = 0.62), IQ (p = 0.57), and performance validity (p-values = 0.10-0.91). We observed no impairment on any CANTAB test in this FMS/FS sample compared to HCs, although the FMS/FS group displayed shorter reaction times on the Emotional Bias task (anger) (p = 0.01, np2 = 0.20). The groups did not differ in subjective performance ratings (p-values 0.15). Whilst CANTAB attentional set-shifting performance (total trials/errors) correlated with subjective performance ratings in HCs (p-values<0.005, rs = -0.85), these correlations were non-significant in the FMS/FS sample (p-values = 0.10-0.13, rs-values = -0.46-0.50). The FMS/FS group reported more daily cognitive complaints than HCs (p = 0.006, g = 0.92), which were associated with subjective performance ratings on CANTAB sustained attention (p = 0.001, rs = -0.74) and working memory tests (p < 0.001, rs = -0.75), and with depression (p = 0.003, rs = 0.70), and somatoform (p = 0.003, rs = 0.70) and psychological dissociation (p-values<0.005, rs-values = 0.67-0.85). CONCLUSIONS: These results suggest a discordance between objective and subjective neurocognitive functioning in this FMS/FS sample, reflecting intact test performance alongside poorer subjective cognitive functioning. Further investigation of neurocognitive functioning in FND subgroups is necessary.

Dissociation and its biological and clinical associations in functional neurological disorder: systematic review and meta-analysis.

BACKGROUND: Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking. AIMS: To systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations. METHOD: We searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle-Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263). RESULTS: Seventy-five studies were eligible (FND n = 3940; control n = 3073), most commonly prospective case-control studies (k = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g = 0.90, 95% CI 0.66-1.14, I2 = 70%) and neurological controls (g = 0.56, 95% CI 0.19-0.92, I2 = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g = 0.94, 95% CI 0.65-1.22, I2 = 42%) and FND samples with motor symptoms (g = 0.40, 95% CI -0.18 to 1.00, I2 = 54%). Somatoform dissociation was elevated in FND versus healthy controls (g = 1.80, 95% CI 1.25-2.34, I2 = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations. CONCLUSIONS: Our findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.

Normal amygdala morphology in dissociative identity disorder.

Studies investigating the structure of the amygdala in relation to dissociation in psychiatric disorders are limited and have reported normal or preserved, increased or decreased global volumes. Thus, a more detailed investigation of the amygdala is warranted. Amygdala global and subregional volumes were compared between individuals with dissociative identity disorder (DID: n = 32) and healthy controls (n = 42). Analyses of covariance did not show volumetric differences between the DID and control groups. Although several unknowns make it challenging to interpret our findings, we propose that the finding of normal amygdala volume is a genuine finding because other studies using this data-set have presented robust morphological aberrations in relation to the diagnosis of DID.

Dissociative identity state-dependent working memory in dissociative identity disorder: a controlled functional magnetic resonance imaging study.

BACKGROUND: Memory function is at the core of the psychopathology of dissociative identity disorder (DID), but little is known about its psychobiological correlates. AIMS: This study aims to investigate whether memory function in DID differs between dissociative identity states. METHOD: Behavioural data and neural activation patterns were assessed in 92 sessions during an n-back working memory task. Participants were people with genuine diagnosed DID (n = 14), DID-simulating controls (n = 16) and a paired control group (post-traumatic stress disorder (n = 16), healthy controls (n = 16)). Both DID groups participated as authentic or simulated neutral and trauma-related identity states. Reaction times and errors of omission were analysed with repeated measures ANOVA. Working memory neural activation (main working memory and linear load) was investigated for effects of identity state, participant group and their interaction. RESULTS: Identity state-dependent behavioural performance and neural activation was found. DID simulators made fewer errors of omission than those with genuine DID. Regarding the prefrontal parietal network, main working memory in the left frontal pole and ventrolateral prefrontal cortex (Brodmann area 44) was activated in all three simulated neutral states, and in trauma-related identity states of DID simulators, but not those with genuine DID or post-traumatic stress disorder; for linear load, trauma-related identity states of those with genuine DID did not engage the parietal regions. CONCLUSIONS: Behavioural performance and neural activation patterns related to working memory in DID are dependent on the dissociative identities involved. The narrowed consciousness of trauma-related identity states, with a proneness to re-experiencing traumatising events, may relate to poorer working memory functioning.