It’s March 5th, the day that folks everywhere who live with the diagnosis of dissociative identity disorder gather to spread awareness.
Research and Essays on DID
To help raise awareness I have made a compilation of some of the papers and essays out there concerning DID. The list is not all comprehensive as there are many more papers out there, but if you are wanting to begin researching DID on your own, this is a good start.
One hint I would give you if you are looking for further research pay close attention to the list of resources at the bottom of any paper.
I am aware that when I copy/pasted the following information that some of the formattings was messed up causing misspelled words etc. Ignore those please, and just enjoy looking up the vital information I’ve provided.
Please, feel free to share these links with your therapists, friends, families and anyone else who is interested in DID.
Are multiple personalities borderline? An analysis of 33 cases. … The authors detail their investigation into the positive relationship between …
The Neurology of Dissociative Identity disorder
The Neuropsychiatry of Dissociative Identity Disorder: Why Split Personality Patients Switch Personalities Intermittently?
Rutkofsky, I. H., Khan, A. S., Sahito, S., Aqeel, N., & Tohid, H. (2017). The Neuropsychiatry of Dissociative Identity Disorder: Why Split Personality Patients Switch Personalities Intermittently. J Cell Sci Ther, 8(267), 2.
DOI: 10.4172/2157-7013. 1000267
Little has been known about the possible brain changes in the patients suffering from the psychiatric illness called Dissociative Identity Disorder (DID). This review suggests that the patients of DID have structural changes in the limbic system – hippocampus and amygdala -and the cortex. Blood flow is also altered in the orbito-frontal cortex.
Another interesting finding of this review is that the glutamate release is found to be the cause of the dissociative symptoms, if this is true, then probably the glutamate blockers is the future for managing such patients. Furthermore, this review also highlights that in some DID patients the dorsolateral prefrontal and parietal cortex are activated. The limbic system especially the amygdala and the dorsolateral prefrontal and parietal cortex are associated with the
short term and working memory, while the hippocampus is associated with long-term memory.
All these regions are somehow affected in the DID patient’s brain. Thus, this explains the symptoms of the multiple personality changes and forgetting about the previous personality. Why the nature of these symptoms is temporary despite evidence for permanent structural brain changes is perhaps a question that is yet to be answered. Future studies will broaden our knowledge about the ‘cyclical nature’ and complete neuropsychiatry of this unique medical illness.
Trauma, PTSD and the Developing Brain
Herringa, R. J. (2017). Trauma, PTSD, and the developing brain. Current psychiatry reports, 19(10), 69.
PTSD in youth is common and debilitating. In contrast to adult PTSD, relatively little is known about the neurobiology of pediatric PTSD, nor how neurodevelopment may be altered. This review summarizes recent neuroimaging studies in pediatric PTSD and discusses implications for future study.
Pediatric PTSD is characterized by abnormal structure and function in neural circuitry supporting threat processing and emotion regulation. Furthermore, cross-sectional studies suggest that youth with PTSD have abnormal frontolimbic development compared to typically developing youth. Examples include declining hippocampal volume, increasing amygdala reactivity, and declining amygdala-prefrontal coupling with age.
Pediatric PTSD is characterized by both overt and developmental abnormalities in frontolimbic circuitry. Notably, abnormal frontolimbic development may contribute to increasing threat reactivity and weaker emotion regulation as youth age. Longitudinal studies of pediatric PTSD are needed to characterize individual outcomes and determine whether current treatments are capable of restoring healthy neurodevelopment.
Frontal and occipital perfusion changes in dissociative identity disorder
Sar, V., Unal, S. N., & Ozturk, E. (2007). Frontal and occipital perfusion changes in dissociative identity disorder. Psychiatry Research: Neuroimaging, 156(3), 217-223.
The aim of the study was to investigate if there were any characteristics of regional cerebral blood flow (rCBF) in dissociative identity disorder.
Twenty-one drug-free patients with dissociative identity disorder and nine healthy volunteers participated in the study. In addition to a clinical evaluation, dissociative psychopathology was assessed using the Structured Clinical Interview for DSM-IV Dissociative Disorders, the Dissociative Experiences Scale and the Clinician-Administered Dissociative States Scale.
A semi-structured interview for borderline personality disorder, the Hamilton Depression Rating Scale, and the Childhood Trauma Questionnaire were also administered to all patients. Normal controls had to be without a history of childhood trauma and without any depressive or dissociative disorder.
Regional cerebral blood flow (rCBF) was studied with single photon emission computed tomography (SPECT) with Tc99m-hexamethylpropylenamine (HMPAO) as a tracer.
Compared with findings in the control group, the rCBF ratio was decreased among patients with dissociative identity disorder in the orbitofrontal region bilaterally. It was increased in median and superior frontal regions and occipital regions bilaterally.
There was no significant correlation between rCBF ratios of the regions of interest and any of the psychopathology scale scores. An explanation for the neurophysiology of dissociative psychopathology has to invoke a comprehensive model of interaction between anterior and posterior brain regions.
Functional Magnetic Resonance Imaging of Personality Switches in Women with Dissociative Identity Disorder
Tsai, G. E., Condie, D., Wu, M. T., & Chang, I. W. (1999). Functional magnetic resonance imaging of personality switches in a woman with dissociative identity disorder. Harvard Review of Psychiatry, 7(2), 119-122.
Dissociative identity disorder (DID) is a controversial condition characterized by fluctuating constellations of affective, memory, and behavioral symptoms that are associated with a changing sense of personal identity.1 Clinically, DID is of-ten associated with posttraumatic stress disorder (PTSD). Psycho-dynamically, it is considered rooted in childhood traumatic experiences and is usually an extreme form of defense against overwhelming abuse.
Researchers have recently reported hippocampal volume to be decreased in persons with PTSD secondary to child-hood abuse.2 The hippocampus is sensitive to stress and ov-erarousal,2 which individuals with DID—like those with PTSD—often encounter in early life. We performed a volumetric study of the hippocampus in a patient with comorbid DID and PTSD for comparison with the literature on PTSD.
Very little is known about the brain substrate involved in DID, particularly the mechanism of personality switch. Neuro-physiological study of DID is limited due to the dynamic nature of the disorder. Although measurable neurophysiological differences among personalities in DID have been re-ported, the results have been inconsistent and often mixed.3
Unlike other brain mapping techniques, functional magnetic resonance imaging (fMRI) has high temporal and spatial resolution,4 so it is an ideal tool to study neuropsychiatric disorders with dynamic symptoms, such as DID. And with fMRI—in contrast to procedures such as positron emission tomography and single photon emission tomography— a subject can be studied repeatedly without the concern of ionizing radiation. To investigate the neuronal substrate involved in the personality switches of DID, we conducted an fMRI study on a woman with DID while she was switching personalities.
Weniger, G., Lange, C., Sachsse, U., & Irle, E. (2008). Amygdala and hippocampal volumes and cognition in adult survivors of childhood abuse with dissociative disorders. Acta Psychiatrica Scandinavica, 118(4), 281-290
Trauma-exposed individuals with post-traumatic stress disorder (PTSD) display reduced amygdala and hippocampal size and impaired cognition. However, studies on trauma-exposed individuals with dissociative amnesia (DA) or dissociative identity disorder (DID) are lacking.
Twenty-three young women who had experienced severe childhood sexual ⁄ physical abuse, diagnosed with DA ⁄ DID or PTSD, and 25 healthy control subjects were subjected to 3D structural magnetic resonance imaging of amygdala and hippocampus and a clinical and neuropsychological investigation.
Compared with controls, trauma-exposed subjects with PTSD (n = 10) displayed significantly reduced amygdala and hippocampal size and significantly impaired cognition. By contrast, trauma-exposed subjects with DA or DID (n = 13) displayed normal amygdala and hippocampal size and normal cognition.
We report for the first-time volumetric results in subjects with DA ⁄ DID without PTSD as comorbid diagnosis. Our results indicate preserved amygdala and hippocampal size and preserved cognition in subjects with these disorders.
Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism
Brand, M., Eggers, C., Reinhold, N., Fujiwara, E., Kessler, J., Heiss, W. D., & Markowitsch, H. J. (2009). Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism. Psychiatry Research: Neuroimaging, 174(1), 32-39.
Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage.
Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical–episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions.
In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits.
However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia.
We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F] fluorodeoxyglucose positron emission tomography (FDG-PET).
Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender.
We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.
Sar, V., Unal, S. N., Kiziltan, E., Kundakci, T., & Ozturk, E. (2001). HMPAO SPECT study of regional cerebral blood flow in dissociative identity disorder. Journal of Trauma & Dissociation, 2(2), 5-25.
The aim of the study was to investigate if there were any characteristics of regional cerebral blood flow (rCBF) in dissociative identity disorder. Fifteen patients with dissociative identity disorder and eight healthy volunteers participated in the study. The clinical diagnosis of dissociative identity disorder was confirmed using the Structured Clinical Interview for DSM-IV Dissociative Disorders. The Structured Clinical Inter- view for DSM-III-R was also administered to all patients to screen comorbid psychiatric conditions.
Regional cerebral blood flow was studied using a SPECT system with Tc99m-hexamethylpropylenamine (HMPAO) as a tracer. The rCBF ratio was decreased in orbitofrontal region bilaterally and increased in left (dominant hemi-sphere) lateral temporal region among patients with dissociative identity disorder when compared to the control group. The structured interview diagnoses of concurrent or life time major depression, PTSD, psychotic dis order, or on-going drug treatment were not significantly related to perfusion in these regions. There was no statistically meaningful difference in rCBF ratios between host and alter personality states.
Our findings suggest that orbitofrontal and left (dominant hemi sphere) lateral temporal regions are affected in dissociative identity disorder.
A replication of this study on a larger group of drug-free dissociative patients and various psychiatric control groups would lead to more definitive findings.
One brain, two selves
Reinders, A. A. T. S., Nijenhuis, E. R., Paans, A. M., Korf, J., Willemsen, A. T. M., & Den Boer, J. A. (2003). One brain, two selves. Neuroimage, 20(4), 2119-2125.
NOTE: Your computer may say the file is dangerous, but it is not. It’s okay to click on the link to the PDF above.
Having a sense of self is an explicit and high level-functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with multiple personality disorder, i.e. dissociative identity disorder (DID).
We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory.
Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.
Toward an Etiology of Dissociative Identity Disorder: A Neurodevelopmental Approach
(you must pay to access)
Forrest, K. A. (2001). Toward an etiology of dissociative identity disorder: A neurodevelopmental approach. Consciousness and Cognition, 10(3), 259-293.
This article elaborates on Putnam’s “discrete behavioral states” model of dissociative identity disorder (Putnam, 1997) by proposing the involvement of the orbitalfrontal cortex in the development of DID and suggesting a potential neurodevelopmental mechanism responsible for the development of multiple representations of self.
The proposed “orbitalfrontal” model integrates and elaborates on theory and research from four domains: the neurobiology of the orbitalfrontal cortex and its protective inhibitory role in the temporal organization of behavior, the development of emotion regulation, the development of the self, and experience-dependent reorganizing neocortical processes.
The hypothesis being proposed is that the experience-dependent maturation of the orbitalfrontal cortex in early abusive environments, characterized by discontinuity in dyadic socio-affective interactions between the infant and the caregiver, may be responsible for a pattern of lateral inhibition between conflicting subsets of self-representations which are normally integrated into a unified self. The basic idea is that the discontinuity in the early caretaking environment is manifested in the discontinuity in the organization of the developing child’s self.
Volume of discrete brain structures in complex dissociative disorders: preliminary findings
Ehling, T., Nijenhuis, E. R. S., & Krikke, A. P. (2007). Volume of discrete brain structures in complex dissociative disorders: preliminary findings. Progress in brain research, 167, 307-310.
Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that:
(1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala than normal controls,
(2) these volumes are associated with severity of psychoform and somatoform dissociative symptoms, and
(3) patients who recovered from dissociative identity disorder (DID) have more hippocampal volume that patients with florid DID.
The preliminary findings of the study are supportive of these hypotheses.
Psychotherapy for dissociative disorders may affect hippocampal volume, but longitudinal studies are required to document this potential causal relationship.
Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder
Schlumpf, Y. R., Nijenhuis, E. R., Chalavi, S., Weder, E. V., Zimmermann, E., Luechinger, R., … & Jäncke, L. (2013). Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder. NeuroImage: Clinical, 3, 54-64.
Objective: The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as “Emotional Parts” (EP), but mentally avoid these as “Apparently Normal Parts” of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently.
Methods: Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures.
Results: Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP bio-psychosocially.
Conclusions: DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP under-activated. The findings support TSDP. Major clinical implications are discussed.
Dissociative Part-Dependent Resting-State Activity in Dissociative Identity Disorder: A Controlled fMRI Perfusion Study
Schlumpf, Y. R., Reinders, A. A., Nijenhuis, E. R., Luechinger, R., van Osch, M. J., & Jäncke, L. (2014). Dissociative part-dependent resting-state activity in dissociative identity disorder: a controlled FMRI perfusion study. PLoS One, 9(6), e98795.
In accordance with the Theory of Structural Dissociation of the Personality (TSDP), studies of dissociative identity disorder (DID) have documented that two prototypical dissociative subsystems of the personality, the “Emotional Part” (EP) and the “Apparently Normal Part” (ANP), have different biopsychosocial reactions to supraliminal and subliminal trauma-related cues and that these reactions cannot be mimicked by fantasy prone healthy controls nor by actors.
Arterial spin labeling perfusion MRI was used to test the hypotheses that ANP and EP in DID have different perfusion patterns in response to rest instructions, and that perfusion is different in actors who were instructed to simulate ANP and EP. In a follow-up study, regional cerebral blood flow of DID patients was compared with the activation pattern of healthy non-simulating controls.
Compared to EP, ANP showed elevated perfusion in bilateral thalamus. Compared to ANP, EP had increased perfusion in the dorsomedial prefrontal cortex, primary somatosensory cortex, and motor-related areas. Perfusion patterns for simulated ANP and EP were different. Fitting their reported role-play strategies, the actors activated brain structures involved in visual mental imagery and empathizing feelings. The follow-up study demonstrated elevated perfusion in the left temporal lobe in DID patients, whereas non-simulating healthy controls had increased activity in areas which mediate the mental construction of past and future episodic events.
DID involves dissociative part-dependent resting-state differences. Compared to ANP, EP activated brain structures involved in self-referencing and sensorimotor actions more. Actors had different perfusion patterns compared to genuine ANP and EP. Comparisons of neural activity for individuals with DID and non-DID simulating controls suggest that the resting-state features of ANP and EP in DID are not due to imagination. The findings are consistent with TSDP and inconsistent with the idea that DID is caused by suggestion, fantasy proneness, and role-playing.
Opposite brain emotion-regulation patterns in identity states of dissociative identity disorder: A PET study and neurobiological model
Reinders, A. A., Willemsen, A. T., den Boer, J. A., Vos, H. P., Veltman, D. J., & Loewenstein, R. J. (2014). Opposite brain emotion-regulation patterns in identity states of dissociative identity disorder: A PET study and neurobiological model. Psychiatry Research: Neuroimaging, 223(3), 236-243.
Imaging studies in posttraumatic stress disorder (PTSD) have shown differing neural network patterns between hypo-aroused/dissociative and hyper-aroused subtypes.
Since dissociative identity disorder (DID) involves different emotional states, this study tests whether DID fits aspects of the differing brain activation patterns in PTSD. While brain activation was monitored using positron emission tomography, DID individuals (n¼11) and matched DID-simulating healthy controls (n¼16) underwent an autobiographic script-driven imagery paradigm in a hypo-aroused and a hyper-aroused identity state.
Results were consistent with those previously found in the two PTSD subtypes for the rostral/dorsal anterior cingulate, the prefrontal cortex, and the amygdala and insula, respectively.
Furthermore, the dissociative identity state uniquely activated the posterior association areas and the para-hippocampal gyri, whereas the hyper-aroused identity state uniquely activated the caudate nucleus.
Therefore, we proposed an extended PTSD-based neurobiological model for emotion modulation in DID: the hypo-aroused identity state activates the prefrontal cortex, cingulate, posterior association areas and para-hippocampal gyri, thereby overmodulating emotion regulation; the hyper-aroused identity state activates the amygdala and insula as well as the dorsal striatum, thereby under modulating emotion regulation.
This confirms the notion that DID is related to PTSD as hypo-aroused and hyper-arousal states in DID and PTSD are similar.
Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study
Elzinga, B. M., Ardon, A. M., Heijnis, M. K., De Ruiter, M. B., Van Dyck, R., & Veltman, D. J. (2007). Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study. Psychological medicine, 37(2), 235-245.
Background. Memory functioning has been highlighted as a central issue in pathological dissociation. In non-pathological dissociation, evidence for enhanced working memory has been found, together with greater task-load related activity. So far, no imaging studies have investigated working memory in dissociative patients.
Method. To assess working memory in dissociative patient’s functional magnetic resonance imaging was used during performance of a parametric, verbal working-memory task in patients with a dissociative disorder (n=16) and healthy controls (n=16).
Results. Imaging data showed that both groups activated brain regions typically involved in working memory, i.e. anterior, dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex. Dissociative patients showed more activation in these areas, particularly in the left anterior PFC, dorsolateral PFC and parietal cortex. In line with these findings, patients made fewer errors with increasing task load compared to controls, despite the fact they felt more anxious and less concentrated during task performance.
Conclusions. These results extend findings in non-pathological high dissociative individuals, suggesting that trait dissociation is associated with enhanced working-memory capacities. This may distinguish dissociative patients from patients with post-traumatic stress disorder, who are generally characterized by impaired working memory.
Aiding the diagnosis of dissociative identity disorder: pattern recognition study of brain biomarkers
Reinders, A. A., Marquand, A. F., Schlumpf, Y. R., Chalavi, S., Vissia, E. M., Nijenhuis, E. R., … & Veltman, D. J. (2018). Aiding the diagnosis of dissociative identity disorder: pattern recognition study of brain biomarkers. The British Journal of Psychiatry, 1-9.
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.
To investigate whether data-driven pattern recognition methodologies applied to structural brain images can provide biomarkers to aid DID diagnosis.
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.
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.
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.
Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States
Reinders, A. S., Willemsen, A. T., Vos, H. P., den Boer, J. A., & Nijenhuis, E. R. (2012). Fact or factitious? A psychobiological study of authentic and simulated dissociative identity states. PLoS One, 7(6), e39279.
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.
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.
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.
The Emerging Psychobiology of Trauma‐Related Dissociation and Dissociative Disorders
(you must pay for access to this book chapter)
Nijenhuis, E. R., van der Hart, O., & Steele, K. (2002). The emerging psychobiology of trauma‐related dissociation and dissociative disorders. Biological psychiatry, 1079-1098.
Psychoform and Somatoform, and Negative and Positive, Dissociative Symptoms
Retraction of the Field of Consciousness and Low Levels of Conscious Awareness
PTSD, Dissociation, and Stress Responses
Possible Involvement of Neurochemicals in Dissociation
Enhancement and Impairment of the Memory Function
Substance‐induced Dissociative‐like Symptoms in Healthy Individuals
Substance‐induced Dissociative Symptoms and States in PTSD Patients
Interactions Among Neuropeptide Y (NPY), Corticotropin‐releasing Factor (CRF), Cortisol, and Norepinephrine
Urinary Catecholamines and CSF Norepinephrine
Key Brain Structures in Integrative Functions
Medial Prefrontal Cortex
Somatosensory Association Areas:
Neurobiological Models of Dissociative Disorders
DID and Epilepsy
Dissociative Disorders and Cerebral Hemispheric Laterality
Dissociative Personalities as Discrete Behavioural States
Dissociative Personalities in DID
The Theory of Structural Dissociation
Emotional Operating Systems
The EP is Dedicated to Survival Under Threat
The ANP Involves Systems That Manage Daily Life and Promote Survival of the Species
Similarities Between the Human and Animal Defensive System
Psychobiological Interference with Integration of ANP and EP
Peritraumatic Integrative Failure
Post‐traumatic Integrative Failure
Psychobiological Research of ANP and EP
Differences Between ANP and EP on Subliminal Threat Exposure
Symptom Provocation by Exposure to Neutral and Trauma Memory Scripts in DID
Positive Feedforward Excitation (EP) and Negative Feedforward Inhibition (ANP)?
EP‐dependent Responsivity to Threat
ANP‐dependent Responsivity to Threat
Psychobiological Differences Among Dissociative Parts of the Personality in PTSD
From the Neuropsychiatric to the Analytic: Three Perspectives on Dissociative Identity Disorder
Biswas, J., Chu, J. A., Perez, D. L., & Gutheil, T. G. (2013). From the neuropsychiatric to the analytic: three perspectives on dissociative identity disorder. Harvard review of psychiatry, 21(1), 41-51.
This paper uses case studies to show the neuropsychiatric and analytic perspectives of DID.
Computers can ‘spot the difference’ between healthy brains and the brains of people with DID
NIHR Maudsley Biomedical Research Centre and published in the British Journal of Psychiatry.
Machine-learning and neuroimaging techniques have been used to accurately distinguish between individuals with Dissociative Identity Disorder (DID) and healthy individuals, on the basis of their brain structure, in new research part funded by the NIHR Maudsley Biomedical Research Centre and published in the British Journal of Psychiatry.
Commenting on the research, Dr Reinders said: “DID diagnosis is controversial and individuals with DID are often misdiagnosed. From the moment of seeking treatment for symptoms, to the time of an accurate diagnosis of DID, individuals receive an average of four misdiagnoses and spend seven years in mental health services.
“The findings of our present study are important because they provide the best evidence of a biological basis for distinguishing between individuals with DID and healthy individuals. Ultimately, the application of pattern recognition techniques could prevent unnecessary answering through earlier and more accurate diagnosis, facilitating faster and more targeted therapeutic interventions.”
The Epigenetic (genetic) Changes from Childhood Trauma
Child Abuse and Epigenetic Mechanisms of Disease Risk
Yang, B. Z., Zhang, H., Ge, W., Weder, N., Douglas-Palumberi, H., Perepletchikova, F., … & Kaufman, J. (2013). Child abuse and epigenetic mechanisms of disease risk. American journal of preventive medicine, 44(2), 101-107.
Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD
Yehuda, R., Flory, J. D., Pratchett, L. C., Buxbaum, J., Ising, M., & Holsboer, F. (2010). Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology, 212(3), 405-417.
Abstract: Rationale Early Life Stress (ELS) increases risk for both adult traumatization and posttraumatic stress disorder (PTSD). Adult PTSD may also reflect a continuation of a response to an earlier exposure to adversity. Given similarities between neuroendocrine aspects of PTSD and ELS, such as in reduced cortisol signaling and glucocorticoid receptor (GR) responsiveness, some aspects of the biology of PTSD may reflect biological correlates of risk.
Objectives: This paper will examine how empirical findings regarding the biological basis of ELS can inform our understanding of the neuroendocrinology of PTSD. This paper will also propose a hypothetical model to guide future research that integrates genetic, epigenetic, neuroendocrine, and psychological observations to understand the contribution of ELS neurobiology to PTSD.
The transmission of traits across generations has typically been attributed to the inheritance by offspring of genomic information from parental generations. However, recent evidence suggests that epigenetic mechanisms are capable of mediating this type of transmission. In the case of maternal care, there is evidence for the behavioral transmission of postpartum behavior from mothers to female offspring.
The neuroendocrine and molecular mediators of this transmission have been explored in rats and implicate estrogen–oxytocin interactions and the differential methylation of hypothalamic estrogen receptors. These maternal effects can influence multiple aspects of neurobiology and behavior of offspring and this particular mode of inheritance is dynamic in response to environmental variation.
In this review, evidence for the generational transmission of maternal care and the mechanisms underlying this transmission will be discussed as will the implications of this inheritance system for offspring development and for the transmission of environmental information from parents to offspring.
Child Abuse, Depression, and Methylation in Genes Involved with Stress, Neural Plasticity, and Brain Circuitry
Weder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., … & O’Loughlin, K. (2014). Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. Journal of the American Academy of Child & Adolescent Psychiatry, 53(4), 417-424.
To determine whether epigenetic markers predict dimensional ratings of depression in maltreated children.
A genome-wide methylation study was completed using the Illumina 450K BeadChip array in 94 maltreated and 96 healthy non-traumatized children with saliva-derived DNA. The 450K Bead Chip does not include any methylation sites in the exact location as sites in candidate genes previously examined in the literature, so a test for replication of prior research findings was not feasible.
Methylation in 3 genes emerged as genome-wide–significant predictors of depression: DNA-Binding Protein Inhibitor ID–3 (ID3); Glutamate Receptor, Ionotropic N-methyl-D-aspartate (NMDA) 1 (GRIN1); and Tubulin Polymerization Promoting Protein (TPPP) (p < 5.0 × 10−7, all analyses). These genes are all biologically relevant with ID3 involved in the stress response, GRIN1 involved in neural plasticity, and TPPP involved in neural circuitry development. Methylation in CpG sites in candidate genes were not predictors of depression at significance levels corrected for whole genome testing, but maltreated and control children did have significantly different β values after Bonferroni correction at multiple methylation sites in these candidate genes (e.g., BDNF, NR3C1, FKBP5).
This study suggests that epigenetic changes in ID3, GRIN1, and TPPP genes, in combination with experiences of maltreatment, may confer risk for depression in children. The study adds to a growing body of literature supporting a role for epigenetic mechanisms in the pathophysiology of stress-related psychiatric disorders. Although epigenetic changes are frequently long lasting, they are not necessarily permanent. Consequently, interventions to reverse the negative biological and behavioral sequelae associated with child maltreatment are briefly discussed.
Oxytocin Receptor Genetic and Epigenetic Variations: Association with Child Abuse and Adult Psychiatric Symptoms
Smearman, E. L., Almli, L. M., Conneely, K. N., Brody, G. H., Sales, J. M., Bradley, B., … & Smith, A. K. (2016). Oxytocin receptor genetic and epigenetic variations: association with child abuse and adult psychiatric symptoms. Child development, 87(1), 122-134.
Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR).
However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. This study therefore sought to (a) assess the role of epigenetics in the link between abuse and psychopathology and (b) begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41 ± 12.8 years).
Overall, 68% of genotypes were associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology.
However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms.
Epigenetic Mechanisms for the Early Environmental Regulation of Hippocampal Glucocorticoid Receptor Gene Expression in Rodents and Humans
Zhang, T. Y., Labonté, B., Wen, X. L., Turecki, G., & Meaney, M. J. (2013). Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans. Neuropsychopharmacology, 38(1), 111.
Parental care influences development across mammals. In humans such influences include effects on phenotypes, such as stress reactivity, which determine individual differences in the vulnerability for affective disorders.
Thus, the adult offspring of rat mothers that show an increased frequency of pup licking/grooming (ie, high LG mothers) show increased hippocampal glucocorticoid receptor (GR) expression and more modest hypothalamic–pituitary–adrenal responses to stress compared with the offspring of low LG mothers.
In humans, childhood maltreatment associates decreased hippocampal GR expression and increased stress responses in adulthood. We review the evidence suggesting that such effects are mediated by epigenetic mechanisms, including DNA methylation and hydroxymethylation across GR promoter regions.
We also present new findings revealing associated histone post-translational modifications of a critical GR promoter in rat hippocampus.
Taken together these existing evidences are consistent with the idea that parental influences establish stable phenotypic variation in the offspring through effects on intracellular signaling pathways that regulate the epigenetic state and function of specific regions of the genome.
Lester, B. M., Tronick, E., Nestler, E., Abel, T., Kosofsky, B., Kuzawa, C. W., … & Reul, J. M. (2011). Behavioral epigenetics. Annals of the New York Academy of Sciences, 1226(1), 14-33.
Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology.
This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level.
How the epigenome contributes to the development of psychiatric disorders
Bredy, T. W., Sun, Y. E., & Kobor, M. S. (2010). How the epigenome contributes to the development of psychiatric disorders. Developmental psychobiology, 52(4), 331-342.
Epigenetics commonly refers to the developmental process by which cellular traits are established and inherited without a change in DNA sequence.
These mechanisms of cellular memory also orchestrate gene expression in the adult brain and recent evidence suggests that the “epigenome” represents a critical interface between environmental signals, activation, repression and maintenance of genomic responses, and persistent behavior.
We here review the current state of knowledge regarding the contribution of the epigenome toward the development of psychiatric disorders.
Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., … & Bradley, B. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the national academy of sciences, 110(20), 8302-8307.
Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genome-wide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD).
Compared with the same trauma-exposed controls (n = 108), gene-expression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%).
These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%).
This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse.
The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment.
These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D’alessio, A. C., Dymov, S., Labonté, B., Szyf, M., … & Meaney, M. J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature neuroscience, 12(3), 342.
Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide.
We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls.
We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription.
These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
Genome-wide Epigenetic Regulation by Early-Life Trauma
Labonté, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., … & Turecki, G. (2012). Genome-wide epigenetic regulation by early-life trauma. Archives of general psychiatry, 69(7), 722-731.
Context Our genome adapts to environmental influences, in part through epigenetic mechanisms, including DNA methylation. Variations in the quality of the early environment are associated with alterations in DNA methylation in rodents, and recent data suggest similar processes in humans in response to early-life adversity.
Objective To determine genome-wide DNA methylation alterations induced by early-life trauma.
Design Genome-wide study of promoter methylation in individuals with severe abuse during childhood.
Patients, Setting, and Main Outcome Measures Promoter DNA methylation levels were profiled using methylated DNA immunoprecipitation followed by microarray hybridization in hippocampal tissue from 41 French-Canadian men (25 with a history of severe childhood abuse and 16 control subjects). Methylation profiles were compared with corresponding genome-wide gene expression profiles obtained by messenger RNA microarrays. Methylation differences between groups were validated on neuronal and nonneuronal DNA fractions isolated by fluorescence-assisted cell sorting. Functional consequences of site-specific promoter methylation were assessed by luciferase assays.
Results We identified 362 differentially methylated promoters in individuals with a history of abuse compared with controls. Among these promoters, 248 showed hypermethylation and 114 demonstrated hypomethylation. Validation and site-specific quantification of DNA methylation in the 5 most hypermethylated gene promoters indicated that methylation differences occurred mainly in the neuronal cellular fraction. Genes involved in cellular/neuronal plasticity were among the most significantly differentially methylated, and, among these, Alsin (ALS2) was the most significant finding. Methylated ALS2 constructs mimicking the methylation state in samples from abused suicide completers showed decreased promoter transcriptional activity associated with decreased hippocampal expression of ALS2 variants.
Conclusion Childhood adversity is associated with epigenetic alterations in the promoters of several genes in hippocampal neurons.