The Neuropsychiatry of Dissociative Identity Disorder


I found the research paper below on, a wonderful site where you can find recently published research about any medical and psychological topic. It speaks of what goes on in the brain of a person living with DID when they change (switch) from one alter to another. There are graphs and charts available, but you’ll need to go to the original article to find them. I hope you find it as fascinating as I did. Shirley


The Neuropsychiatry of Dissociative Identity Disorder: Why Split Personality Patients Switch Personalities Intermittently


Ian Hunter Rutkofsky, Anser Saeed Khan, Sindhu Sahito, Noorulain Aqeel, and Hassaan Tohid

Link to Article


Little is 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 of 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.

Keywords  Neuropsychiatry;   Psychiatric  illness;  Parietal   cortex; Hippocampus


A 17-year-old female patient was seen in a psychiatric ward at a local hospital in California, USA, she could change her voice anytime and claimed to be possessed by demons occasionally, while sometimes she believed she was a 70-year-old catholic nun, and other times she was in her usual self and sometimes she thought she was a 28-year-old man  named  Victor. She could  speak multiple  languages and  while switching from  one  voice to  another,  she could totally change her personality. She was belligerent and verbally abusive toward the paramedics,  doctors  and  the  nurses.  She refused  to  undergo  any medical treatment despite being belligerent. To keep her calm, she was given the IV haloperidol, which temporarily calmed her down. She was released from the hospital when she felt a little better. While her family sought the help of a local church for a possible exorcism, and ignored medical treatment, the girl eventually died of dehydration few months later.

The above-mentioned case is a typical example of a mental disorder- what we call today, as dissociative identity disorder (DID), previously known as split personality disorder or multiple personality disorder. People suffering from DID may have two or more distinct personalities with possibly different ages, gender and culture [1]. Each personality has  its  own  features  and  characteristics. DID  is one  of  the  most interesting yet one of the least understood pathologies. Modern science is expanding  the  knowledge to  help future  scientists explore more about the possible causes and mechanism behind this disorder. Regarding the involvement of brain, few studies have hinted and given stress and changes in the volume of stress specific regulatory structures of the brain. Upon our review, numerous  studies proposed that the most significant precipitating factors associated with DID is childhood trauma.  Thus, leaving us with the question, does childhood trauma lead to changes in the volume of the hippocampus and the amygdala? In order to find this answer additional neurological research is needed in collaboration with radiological studies.

A Magnetic Resonance Imaging (MRI) study by Vermetten, et al. compared the brain structure of female patients diagnosed with DID with healthy subjects. This study provided the evidence for changes in the limbic system. The hippocampus  and amygdala in DID patients were found to be remarkably smaller (19.2% and 31.6%, respectively). The Amygdala controls  emotions  while the  hippocampus  controls long-term memory, thus Vermetten’s study does provide a logical explanation for the pathophysiology of DID [3].

However, another  MRI study of the hippocampus  and  amygdala demonstrated volume reduction in patients with Post Traumatic Stress Disorder  (PTSD), while no considerable difference was seen in the hippocampus  and  amygdala of Dissociate Amnesia (DA), DA/DID patients or normal subjects [4]. Borderline personality disorder, on the other hand is also a known psychopathology associated with early-age trauma [5]. Investigations also indicate that patients with Borderline personality   disorder   have   smaller   hippocampal   and   amygdalar volumes [6-8]. There has long been a debate about the validity of DID as a mental disorder. Some scholars have suggested that DID is actually fantasy proneness while other scholars argue that all patients with DID have been exposed to early age trauma in their history [9-16]. Vermetten et al. [3] counter argued the MRI study by Weniger et al. by claiming, “patients  with  true  dissociative identity  disorder  without PTSD essentially do not exist” [3]. What early age PTSD, Borderline personality disorder and DID all have in common is a disruption  in early childhood development. In addition to the anatomical change in the volume of these regions of the brain, differences in the biochemical response  to  trauma  have also been  observed in  the  cortico-limbic system.

Animal  models  have  shown  that  glutamate  is  released  in  the cortico-limbic system during stress, and may lead to neurotoxicity and behavioral changes with transient dissociation. Glutamate release may also be responsible for inducing changes in neural plasticity. Similarly, N-Methyl-D-Aspartate (NMDA) antagonists have been used in similar animal models resulting in glutamate secretion. Investigations using NMDA antagonists such as ketamine, indeed do stimulate the release of glutamate in humans thus likely producing the associated trance- like dissociative state. Drugs that inhibit Glutamate should be investigated to elucidate its potential for early intervention in patients with traumatic events [17]. Flashbacks with vivid memories are diagnostic of PTSD. We speculate that with every vivid memory or flashback, glutamate  release  can  result  in  long-term  potentiation, offering a possible explanation for the biochemical mechanism of DID. This postulation further supports Vermetten et al’s claim that patients with true  dissociative identity disorder  do not  exist without  PTSD. Acute Stress Disorder (ASD) follows the same diagnostic guidelines as for PTSD, except for the timeline. ASD takes place within the first month  after the identifiable stressor. If the symptoms persist beyond one month, the diagnosis is considered PTSD. We believe a glutamate blocker  may  have the  greatest  effect in  preventing  neuroplasticity changes in the hippocampus and amygdala and lower the incidence of PTSD cases and  limit  the  progression  to  DID if the  patient  starts treatment  during  the ASD period. Ketamine has become a popular medication in the study of treating acute suicidal ideation; however, a study by M. Schönenberg et al. found that Ketamine aggravates symptoms of acute stress disorder three days post-event with increased symptoms  of  dissociation,  flashbacks, hyperarousal  and  avoidance relative to the comparison groups [18]. Riluzole is a glutamate blocker and currently- FDA approved in the treatment of ALS. Interestingly, a Pilot Study at Yale University, is currently investigating the safety and efficacy of the glutamate blocker in patients with PTSD. The results of this 4-year experiment are expected to be released in 2018 and we will follow these results. However, more studies are needed to explore the relationship of glutamate in the neuronal  circuitry of DID patients.

This can be a potential target for intervention in DID. Depending on how glutamate levels are changed in this disorder, there does exist a possibility – that glutamate blockers administration  targeted therapy may be used in the future to normalize the high levels of glutamate in the  brain.  However, it  is still premature  to  recommend  any  such therapy until  future  clinical trials provide the evidence consistently regarding the efficacy of this nature of treatment.

Working memory involves certain regions in the brain, more specifically the dorsolateral prefrontal and parietal cortex. Elzinga et al. [19], studied these regions of working memory in 16 patients with DID or dissociative disorder not otherwise specified (DDNOS). He found that the patients demonstrated  increased activation in these regions when compared to a control group. In addition, the patients also made fewer errors,  increased  task,  were  more  anxious  and  had  poorer concentration in comparison to the controls.

 Cerebral blood flow and DID

According to Sar et al. regional Cerebral Blood Flow (rCBF) was reduced in the bilateral orbitofrontal  cortex (OFC) in the brains of DID patients. This is similar to the findings in patients with Attention Deficit Disorder  (ADD). Furthermore,  rCBF was augmented  to the median and superior frontal regions and occipital lobes bilaterally [20]. “Decision making capacity has long been associated with the OFC. Considering this, Sar et al. stated that reduced functioning of the OFC leads to impulsivity and in patients with DID could express itself in the form of a new personality with impulsive behavior. Cerebral blood flow of  DID  patients  has  been  studied  by  various  investigations. Reinders et  al. [21] calculated rCBF of DID  patients  in  a neutral personality state (NPS) and compared it with a traumatic personality state (TPS). These subjects were then instructed to listen to a memory script. Interestingly, no differences were recorded between the NPS and TPS when listening to the neutral script. However, while listening to the traumatic script a deactivation pattern of brain areas in the NPS was present. The study concluded – that on a neurobiological level, the patients  with  DID  possess  different  autobiographical  selves. The medial prefrontal cortex was among the brain’s region that was deactivated in the NPS versus TPS experiment. Furthermore, considering the OFC is part of the prefrontal cortex, this study points towards an idea about the involvement of the OFC in patients with DID [22]. In a previous study by Sar et al. showed that  rCBF was reduced in the left and right OFC in DID patients but higher in their left (dominant)  lateral temporal lobe [22]. Some other authors have also discussed the  OFC involvement  [22-24]. In  another  study  by Reinder et al. [25], rCBF data demonstrated different neural networks to be linked with different processing of the neutral and trauma-related memory script by NIS and TIS. They found that patients with their own access to autobiographical trauma-related memory had variations in brain activations in distinct mental states of self-awareness [25]. It is quite clear from the discussion above that there are some alterations in the  brain  structure  of  the  patients  suffering from  this  mysterious psychiatric disorder. It is interesting to note that despite the permanent structural  changes, the symptoms of DID like loss of memory  and recurring personality switch overs are temporary in nature, a bewildering enigma. Much research is needed to unravel the cyclical nature of this disorder.


The neuropsychiatry of dissociative identity disorder (DID) has long been in debate. Scientific community  and  the religious community have differed with each other on the exact nature of the disorder. The scientific community  believes it to be a mental condition  while the religious community believes it as a spiritual phenomenon. Our review suggests that DID is a pathophysiological disorder and brain structural and chemical changes are seen in the DID patients. The limbic system – Amygdala and  hippocampus  are  affected as  explained  by  various authors and scholars. Moreover, an increased activation in the dorsolateral prefrontal and parietal cortex is also seen in some DID patients.  The involvement  of the  limbic system & the  dorsolateral prefrontal  and  parietal cortex (all these regions are associated with short-term  and long term memory), possibly explains the main symptom of changing the personality and forgetting totally about the previous personality. The size of the hippocampus of DID patients is decreased in DID. While some changes in the orbitofrontal cortex are observed- with  reduction  in  functioning  and  the  blood  flow. This suggests other possible symptoms like the changes in personality and the thought process. We also underscored the role of the neurotransmitter  glutamate as a possible cause for the symptoms of dissociation. More studies need to elucidate this relationship. Depending on how this relationship unfolds, it can make a potential target for intervention  in DID via glutamate blockers, if glutamate levels are  found  to  be  increased  in  DID  as  our  review suggests. However, as mentioned above, it is still premature to recommend such a treatment.  These kinds of findings can certainly be helpful for the psychiatrists, neuroscientists as well as the patients. Despite various studies, a challenging question still remains unanswered; like why the disorder presents with temporary amnesia rather than permanent memory loss specially when there is documented  evidence for structural changes in the brain. We recommend  more studies in the near future, to understand  more about the neuropsychiatry and the pathophysiological mechanism for the cyclical nature  of this clinical mystery.


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