A Dynorphin Hypothesis for Dissociative Identity Disorder

A Dynorphin Hypothesis for Dissociative Identity Disorder

Dissociative identity disorder (DID) is a condition that is not well understood, is under-researched, and is controversial. Research and hypotheses on the neurobiology of DID is somewhat limited, and there is little direct empirical evidence that DID does or doesn’t involve alterations to different neurotransmitter systems. Using a comparative psychopharmacological approach, I put forth a novel hypothesis for the etiology of DID involving the k-Opioid system and the endogenous k-Opioid receptor agonist dynorphin, which can explain the phenomenon of alters, the comorbidity of DID with other mental disorders, and characteristics of DID which have not been adequately accounted for by previous models, such as the high frequency of psychotic symptoms in DID. Alters can be understood as an extreme form of dissociation involving identity replacement which exists on a continuum with milder dissociation that does not involve identity replacement. The k-Opioid agonist Salvia Divinorum is able to produce states replicating dissociation, including amnesia, identity replacement, and perceptual experiences associated with DID. 


Similarities Between Salvia Experiences and Dissociative Identity Disorder


Symptoms and unique features of DID share remarkable similarity with the effects of the hallucinogenic, dissociative plant Salvia Divinorum, which is a potent k-Opioid receptor agonist [2]. Salvia is known to produce a unique alteration in one's sense of self, in which upon the onset of the drug the individual will lose their sense of identity and self and replace it with a new identity, complete with distinct memories and personality characteristics, which remains until the drug wears off [2,3,4]. Individuals have little memory of their experiences while under the influence of salvia, and may say unusual things and act in unusual ways, which the individual does not remember [2,3]. The experience of salvia involves significant anxiety and distress, profound depersonalization, derealization, alterations in sense of time, thought insertion delusions, and out of body experiences [2,3,4]. Additionally, salvia causes visual and auditory hallucinations [2,3,4]. Alters in DID, like identity alterations produced by saliva, have distinct memories and personality characteristics [17], and persons with DID are found to have amnesia (though not complete) for events that happened while different alters from the host or current alter were fronting [18], as is found with salvia, in that it almost completely blocks recollection of long term memories during the experience, and individuals have difficulty remembering salvia experiences when the drug wears off [2,3]. Significant changes in behavior are found for dissociative states in DID associated with alters [14,17], similar to the unusual, disinhibited behavior that often occurs under the influence of salvia. Persons with DID experience high levels of depersonalization, derealization, out of body experiences, alterations in sense of time, and Schneiderian delusions like thought insertion [1], which are also characteristic of salvia’s effects. Persons with DID show high levels of hallucinations and delusions [1,6], which are produced by salvia.


Dynorphin, Stress, Trauma, and Comorbidity


Dynorphin is a neurotransmitter released in response to stress, and activates a fear emotional and behavioral response, as well as analgesia and dissociation which may help to deal with stressors [12]. It is shown to be involved in conditioned fear memory, and k-Opioid receptor signaling increases in memory related brain regions in response to trauma [12]. Dissociative identity disorder shows a high rate of comorbidity with other mental disorders. Particularly, DID shows a strong association with other dissociative disorders [1], borderline personality disorder [5,7], schizophrenia and psychosis [9,10], PTSD [13], depression and anxiety disorders [9], and substance use disorders [9]. Changes and increases in dynorphin signaling are strongly associated with and involved in the cause of dissociative disorders, depression and anxiety disorders, PTSD, substance abuse disorders [12,16], schizophrenia & psychosis [11], and borderline personality disorder [8] (there is a lack of direct empirical evidence for dynorphin’s involvement in BPD). DID has been considered as an extreme form of PTSD [19]. Episodes of dissociation and alter switches in DID can be triggered by stress and traumatic memories, which parallels the release of dynorphin in response to stress, and involvement in conditioned fear memory responses. Severe trauma seems to be the primary factor linked to the development of DID. Dynorphin is released during stressful experiences, and the extent to which it is released is increased in traumatic experiences involving inescapable stress which results in dissociative states that serve to reduce the harmful effects of intense, inescapable stress [12]. Similarly, in DID, alters seem to function as a defense and “protection” against the threats faced in traumatic experiences [17]. 


Dissociation, Dynorphin, and Alters


If dissociation occurs during traumatic experiences to suppress the harmful effects of severe and inescapable stress, which leads to repeated dissociation episodes after the event often brought on by memory-related triggers, could more severe trauma cause dissociation to the point of identity replacement, which is re-experienced upon memory-related triggers? The evidence provided in this paper supports this hypothesis. I argue that dissociative amnesic states of identity replacement which characterize DID exist on a continuum with milder dissociative states that do not involve identity replacement. k-Opioid agonists are known to produce psychological effects that mimic stress and trauma, such as anxiety, low mood, dissociation, memory impairment, low self esteem, and trauma symptoms characteristic of DID, such as hallucinations, schneiderian delusions, and identity replacement. During a traumatic experience, dissociation and dynorphin release could occur at such intensity that it produces a state of identity replacement, and this identity replacement could become part of the memory, which could lead to taking on the same identity when triggered, along with flashbacks which commonly occur in DID [1]. Different traumatic events could lead to the formation of multiple distinct associated identities associated with specific triggers to the traumatic event. Alternatively, the content of identity replacement could be dependent on the characteristics of the situation causing the trauma, which could lead to a similar identity being produced by a triggered dissociative state. This is supported by anecdotal reports of salvia experiences, where the identity replacement produced by salvia often relates to the surrounding environment and setting. 


Conclusion


If this hypothesis is true, it has implications for the conceptualization, treatment, diagnosis, and study of DID. It suggests that DID may not be a categorically distinct condition from other dissociative and trauma related disorders, and suggests that - like other disorders such as psychosis and dissociation - it exists on a continuum with 'typical' brain function and experience. It also suggests that similar k-Opioid based pharmacological treatments being explored for disorders such as PTSD and depression could be used to treat DID. Future research on DID should investigate differences in dynorphin signaling in subjects with DID, experimental studies in patients & healthy subjects with pharmacological manipulation of the k-Opioid system could further clarify whether k-Opioid agonists can replicate DID like states, and trigger alter switching. Like the closely related disorders PTSD [20], BPD [21], other dissociative disorders [22], depression & anxiety [23], and substance use disorders [24], this model suggests a high likelihood of a significant genetic component to DID. This also implies that, like the disorders mentioned except for PTSD, it may be possible for "endogenous" (i.e., not caused by trauma) DID to exist, however this is highly speculative. 



A basic dimensional model depicting the effects of different levels of stress on dynorphin signaling, and associated psychological changes. 





  1. Dell (2002) Dissociative Phenomenology of Dissociative Identity Disorder

  2. Sumnall et al. (2010) Salvia divinorum use and phenomenology: results from an online survey

  3. psychonautwiki.org/wiki/Salvinorin_A (retrieved 2023) “Salvinorin A” 

(note) psychonautwiki characterizes the subjective effects of substances based on the wide body of anecdotal experience reports available online, and the experiences of contributors

  1. Gonzalez et al. (2006) Pattern of use and subjective effects of Salvia divinorum among recreational users

  2. Ellason et al. (1995) Assessment of dissociative identity disorder with the Millon Clinical Multiaxial Inventory–II

  3. Ellason & Ross (1995) Positive and negative symptoms in dissociative identity disorder and schizophrenia: A comparative analysis

  4. Dell (1998) Axis II Pathology in Outpatients with Dissociative Identity Disorder

  5. Schmahl et al. (2002) Neurobiological correlates of borderline personality disorder

  6. Ellason et al. (1996) Lifetime axis I and II comorbidity and childhood trauma history in dissociative identity disorder

  7. Renard et al. (2017) Unique and Overlapping Symptoms in Schizophrenia Spectrum and Dissociative Disorders in Relation to Models of Psychopathology: A Systematic Review

  8. Clark & Abi-Dargham (2019) The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence

  9. Leconte et al. (2022) Traumatic stress-induced vulnerability to addiction: critical role of the dynorphin/kappa opioid receptor system

  10. Rodewald et al. (2011) Axis-I comorbidity in female patients with dissociative identity disorder and dissociative identity disorder not otherwise specified

  11. Putnam (1997) Dissociation in children and adolescents: A developmental perspective.

  12. McAllister (2000) Dissociative identity disorder: a literature review

  13. Knoll & Carlezon (2010) Dynorphin, stress, and depression

  14. Watkins & Watkins (1988) The management of malevolent ego states in multiple personality disorder

  15. Huntjens et al. (2012) Inter-Identity Autobiographical Amnesia in Patients with Dissociative Identity Disorder

  16. Brand et al. (2009) Psychological assessment of patients with dissociative identity disorder

  17. Nievergelt et al. (2019) International meta-analysis of PTSD genome-wide association studies identifies sex-and ancestry-specific genetic risk loci

  18. Distel et al. (2009) The Five-Factor Model of Personality and Borderline Personality Disorder: A Genetic Analysis of Comorbidity

  19. Jang et al. (1998) Twin Study of Dissociative Experience

  20. Guffanti et al. (2016) Heritability of major depressive and comorbid anxiety disorders in multi‐generational families at high risk for depression

  21. Carmelli et al. (1990) Heritability of substance use in the NAS-NRC Twin Registry

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