# Textbook of Psychiatry/Dissociative Disorders/Pathogenesis

The research regarding etiology of Dissociative Disorders is controversial. Several factors make it difficult to perform, especially the high co-morbidity of Dissociative Disorders with other psychiatric pathologies. The dissociation may be observed as a transient phenomenon secondary to a medical condition such as temporal lobe epilepsy (Bob, 2007). In addition, dissociative symptoms may be a part of the symptomatology of Substance Abuse, Borderline Personality Disorder, or Obsessive Compulsive Disorder. Some researchers even argue that Dissociative Disorders don’t exist as separate diagnoses at all and should be considered a part of post-traumatic psychopathology. As a general consensus, a link between dissociative symptoms in adulthood and self-reports of childhood traumatic events (including familial loss in childhood, sexual/physical abuse and neglect) has been documented.

## Biological Factors

GENETICS
To date, not many studies have been done to determine the genetic predisposition to Dissociative Disorders. Results of existing studies confirm that the dissociation may be partially genetically determined, although results of twin studies are controversial. One study, by Waller, 1997, found no evidence and another study, by Jang, 1998, found 48% to 55% genetic influence. A study by Savitz, 2008, found that there is involvement of COMT Val158Met polymorphism in mediating the relationship between pre-existing trauma and following development of dissociative psychopathology.
NEUROBIOLOGY
In the area of neurobiological research, multiple studies were done that confirm the presence of physiological changes associated with dissociative symptoms. As already mentioned, there is a hypothesis that early psychological trauma or abuse (i.e., stress) can mediate the development of those changes. To date, several neurotransmitter systems have been implicated in the development of Dissociative Disorders: Hypothalamo-Pituitary-Adrenal Dysfunction (HPA), Glutamate/N-methyl-D-aspartate (NMDA) receptor, Serotonin 5-HT2a, 5-HT2c, ?-aminobutyric acid (GABA), and Opioid receptors.
The HPA axis is known to play a central role in medicating the stress response. Several studies on this have been done to date. Most of them presented similar findings showing that individuals with dissociative symptoms have basal HPA-axis hyperactivity with elevated cortisol and diminished pituitary negative-feedback inhibition (Simeon, 2006).
As an extension of this dysregulation due to stress, some research was performed using neuroimaging. In both animal and human studies, stress at a young age has been shown to be associated with changes in the structure of the hippocampus. Smaller hippocampal and amygdalar volumes in patients with dissociative symptoms have been reported by some researchers (Vermetten, 2006). Decreased hippocampal volume may be explained by stress exposure; the hippocampus is a major target organ for glucocorticoids, which are released during stressful experiences, and prolonged exposure to glucocorticoids can lead to progressive atrophy of the hippocampus. The exact mechanism that can lead to smaller amygdalar volume is unclear. It is possible that other neurotransmitters play a role in this change. In their study, D’Souza et al. (2006) proposed that dissociative symptoms, similar to psychosis, may be related to the inhibitory (GABAergic) deficits that cause unopposed stimulation of serotonin receptors. Lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) work as agonists of serotonin 5-HT2a and 5-HT2c receptors, again suggesting a possible mediating role for serotonin in dissociation.
A similar mechanism might underlie cognitive effects of NMDA receptor antagonists, such as ketamine, which was found to cause a profound dissociative state in healthy individuals. NMDA receptors are widely distributed in the cortex, as well as in the hippocampus and the amygdala; therefore, it is possible that diminished NMDA-related neurotransmission may be related to dissociative states. The effect of cannabinoids confirm this hypothesis, as they have been shown to block NMDA receptors at sites distinct from other noncompetitive NMDA antagonists (Feigenbaum, 1989) and still cause dissociative symptoms.
Several studies using positron emission tomography have been performed. One showed that depersonalization severity was correlated with an increase in cerebral blood flow (CBF) in the right frontal cortex and anterior cingulate, and a decrease in subcortical flow in the amygdala, hippocampus, basal ganglia and thalamus (Mathew, 1999). Reinders (2006) found psychobiological differences for the different dissociative identity states. Regional cerebral blood flow (rCBF) data revealed different neural networks to be associated with different processing of the neutral and trauma-related memory script. Sar et al. (2001, 2007) demonstrated decreased bilateral perfusion in frontal and occipital regions among patients with dissociative identity disorder (DID) compared with a group of non-traumatized healthy individuals, which the researchers think provides some validation of the existence of dissociative identity disorder as a distinct diagnostic category. These results also confirm the "orbito-frontal model" of Dissociative Identitiy Disorder proposed by Forrest (2001), which hypothesizes that the orbito-frontal cortex plays a critical role in the development of dissociative identities due to its inhibitory function. Research regarding the neurobiology of dissociative disorders is ongoing and continues.

## Psychological Factors

There is growing interest in the role of early childhood disturbances of attachment and parenting in the development of dissociation (Dutra, 2009). From that article: "Bowlby, in 1973, suggested that infants may internalize dissociated or unintegrated internal working models of their primary caretakers, as well as of themselves. Main and Solomon (1990) then documented the existence of contradictory, confused, and disoriented behavior among some infants in the presence of the parent when needing comfort. These were termed disorganized/disoriented attachment behaviors. Subsequent meta-analyses have confirmed the association between infant disorganized attachment behavior, parental maltreatment, parental psychopathology, disturbed parent-infant interaction, and childhood behavior problems (Madigan et al. 2006; van IJzendoorn et al. 1999). Liotti (1992) further noted that there are suggestive parallels between infant disorganization and adult dissociation in that both phenomena reflect a pervasive lack of mental or behavioral integration." As discussed above in the "Biological Factors" section, early childhood trauma, loss or abuse are strongly correlated with the development of dissociative symptom. Along with the traumagenic theory of development of dissociative disorders, especially Dissociative Identity Disorder (DID), there are iatrogenic and pseudogenic positions (Reinders, 2006). The iatrogenic position takes the view that Dissociative Identity Disorder symptoms are often induced during psychotherapeutic treatment where there is good therapeutic alliance, high therapeutic dependency and high suggestibility. Therapy may contribute to the creation of false memories, and then separate and distinct identities, leading to the creation of Dissociative Identity Disorder phenomena. Laney and Loftus (2005) and Loftus and Davis (2006) describe cases where individuals that claimed to be amnestic had false memories that were "reconstructed" during therapy. Pseudogenic Dissociative Identity Disorder includes subjects who are simulating DID without any therapeutic intervention. It is a conscious process used for achieving secondary gain.

## Social/Cultural Factors

CULTURAL FACTORS
There is a growing body of research targeted at possible cultural differences, significance of the place of origin or other ethnical background in the development of dissociative disorders. Racial and ethnic differences were studied by Douglas (2009) in a non-clinical population and the results indicated differences in dissociation as a function of race: Africans and Asian Americans reported significantly higher rates of dissociation compared to Whites. A substantial proportion of recently published cases of dissociative disorders showed that immigration is an important factor in the development of DID (Staniloiu, 2009). Fatalism, trance, possession, spiritual and healing practices (Seligman, 2008; Moreira-Almeida A, 2008) are being studied. All this research can advance the ethnographic studies of dissociation and highlights the importance of social and cultural aspects of its development.
JURISPRUDENCE
One of the social aspects of debate is implication of DID in jurisprudence. This illustrates how iatrogenic and pseudogenic theories of development DID may be implicated. There are three categories of legal complications related to the diagnosis of dissociative disorders that the court system has to deal with (Reinders, 2006). Firstly, the individual suffering from DID may accuse another person of sexual or physical abuse. Secondly, the individual suffering form DID may claim not to be responsible for crimes committed in a different identity state. And, thirdly, if a person has multiple identities, which one can legally represent that person?
FAMILIES
To date, several family environmental factors were found to be associated with dissociation, including lack of parental care and warmth (Mann and Sanders, 1994; Modestin et al. 2002), inconsistent discipline (Braun and Sachs, 1985; Mann and Sanders, 1994), and poor relationship between parents (Maaranen et al. 2004). Additionally, all of these factors were also associated with abusive environments (Wolfe, 1985). Familial and social support should be recognized as important protective factors against the development of DID (Korol, 2008).