Neurobiology of Depersonalization Disorder (Ch. 22 Dell) Flashcards
Ch. 22 Dell
What are the four classes of chemicals consistently implicated in inducing depersonalization in healthy subjects?
The four classes of chemicals consistently implicated in inducing depersonalization in healthy subjects are 1. NMDA antagonists 2. cannabinoids 3. hallucinogens 4. opioid agonists.
Ch. 22 Dell
Describe the ketamine induction of depersonalization?
The NMDA antagonist ketamine induces a profound dissociative state in healthy subjects that has been likened to the negative symptoms of schizophrenia The medication lamotrigine attenuates ketamine-induced dissociation by inhibiting the release of glutamate.
Ch. 22 Dell
Where are NMDA receptors located?
NMDA receptors are widely distributed in the cortex, and well as in the hippocampus and the amygdala, and are thought to mediate associative functioning, among other things.
Ch. 22 Dell
What is a proposed method behind the cannabinoid induction of depersonalization?
Cannabinoids can induce depersonalization, with a pronounced component of temporal disintegration. In addition to their action at the CB receptors, cannabinoids have been shown to block NMDA receptors at sites distinct from other noncompetitive NMDA antagonists. Thus, their dissociative effect might in fact be mediated via the NMDA receptor.
Ch. 22 Dell
What is the connection between the autonomic system and depersonalization
There is some evidence for autonomic blunting in depersonalization, especially DPD.
Ch. 22 Dell
What is the connection between the HPA-axis and depersonalization?
The hypothalamic-pituitary-adrenal (HPA) axis is known to play a central role in mediating the stress response 2 studies show diminished HPA axis sensitivity in DPD patients.
-HPA axis dysregulation may be present, characterized by baseline heightened activity yet blunted reactivity to stress.
DNTM: A study of the HPA axis in DPD compared to healthy controls found a tendency for elevated basal urinary and plasma cortisol in DPD compared to controls, with a highly statistically significant resistance to low-dose dexamethasone suppression, suggesting diminished HPA axis sensitivity
Ch. 22 Dell
What are 3 proposed models underlying depersonalization?
- Depersonalization from the superior and middle temporal gyrus. -DNTM: described “queer sensations of not being present and floating away, … far off and out of this world”. They postulated that these “illusions of unfamiliarity and strangeness” involved an “alteration in the usual mechanism of comparison of immediate sensory perceptions with memory records” 2. the “corticolimbic disconnection hypothesis.” -It proposed bilateral corticolimbic disconnection with prefrontal activation and limbic inhibition, resulting in hypoemotionality (via amygdalar inhibition) as well as attentional difficulties (via cingulate inhibition). 3. disintegration of various brain areas -proposed that the integration of various cortical areas may be necessary for cohesive conscious experience, -dissociation may involve disruption of corticocortical, thalamocortical, amygdalocortical, and hippocampocortical connectivity. -corticocortical connectivity may be NMDA-receptor-mediated. These models are clearly not mutually exclusive
Ch. 22 Dell
How do (some) chronic depersonalization experiences differ from acute depersonalization?
Acute depersonalization precipitated by severe or life-threatening stress may be viewed as adaptive, allowing the individual emotional distance and detachment from circumstances that might otherwise be overwhelming. Chronic depersonalization symptoms that become autonomous of the original stressful triggers are clearly maladaptive, and suggest dysregulated brain functioning that has failed to reestablish homeostasis.
Ch. 22 Dell
Which brain areas are related to depersonalization in seizure and tumor patients?
These suggest a unique role for the inferior parietal lobule and other transmodal sensory cortical areas in mediating depersonalization-like experiences: 1. Depersonalization is common in seizure patients, especially in temporal lobe epilepsy with left- sided foci. 2. Inferior parietal and angular gyrus tumors can manifest with depersonalization symptoms 4. In patients with parietal lobe epilepsy, frequent somatosensory aurae, disturbances of body image, vertiginous sensations, and visual illusions were reported
Ch. 22 Dell
Describe 3 studies of chemical-induced depersonalization.
A PET study using IV marijuana found that cerebral blood flow increase in the right frontal and anterior cingulate correlated with depersonalization severity, while there was subcortical CBF decrease in amygdala, hippocampus, basal ganglia, and thalamus. A PET imaging study with the hallucinogenic 5HT1A/2A agonist psilocybin resulted in increased dopamine in striatum that correlated with depersonalization severity, but there was also prominent mood and psychotic symptom induction. Finally, an FDG-PET study using high-dose amphetamine found increased metabolism in the anterior cingulate, striatum, and thalamus; however, mania was more prominent than depersonalization in these subjects. It can readily be seen that the findings of these three studies are partly in accord and partly contradictory of the three models previously outlined
Ch. 22 Dell
What are the core features of depersonalization?
The subjective sense of unfamiliarity is central to the depersonalization experience. That is, if an incoming perception is not processed as familiar, it will be experienced as unreal, strange, detached, or unemotional. Therefore depersonalization may be characterized by key disturbances in areas of the brain responsible for matching incoming sensory information to preexisting memory networks of these percepts, involving both limbic structures and sensory association cortical areas.
Ch. 22 Dell
What were the results of the study of dissociated PTSD subjects?
Lanius et al. (2002) studied women with PTSD secondary to childhood sexual abuse, using fMRI with traumatic script-driven imagery. Of the PTSD subjects, about 30% dissociated in response to the scripts. The dissociative state was associated with increased activation in the medial prefrontal cortex (BA 9,10) and inferior frontal gyrus (BA 47), the anterior cingulate (BA 24 and 32), the superior and middle temporal gyri (BA 38), the parietal lobe (BA 7), and the occipital lobe (BA 19). This pattern of activation is similar to that of two imaging studies in DPD described in the following.
Ch. 22 Dell
What were the results of the first of 2 DPD studies?
In an fMRI study, three groups were compared (DPD, OCD, and normals) in their responses to neutral and aversive visual stimuli. DPD patients rated the aversive pictures as less emotive than OCD and Normal patients. Also, DPD patients, in response to the aversive pictures, did not activate the insula (part of the limbic system that is the center for disgust) and showed heightened activation in the right ventral prefrontal cortex. These findings suggested a neural mechanism for emotional detachment that is mediated by prefrontal activation and limbic inhibition.
Ch. 22 Dell
What were the results of the 2nd of 2 DPD studies?
In a PET study of DPD: -Post-hoc analyses revealed that the DPD group had significantly lower activity in right temporal BA 22 and 21, higher activity in parietal BA 7B and 39, and higher activity in left occipital BA 19. -Dissociation scores were very strongly correlated with BA 7B activity. -Interestingly, all of these areas of dysfunction are components of the sensory cortex. -Brodmann area 22 is an auditory association area -area 19 is a visual association area responsible for visual integration and depth perception -area 7B is a somatosensory association area responsible for somatosensory integration. -Area 39 (the angular gyrus) is a multimodal associative area in the inferior parietal lobule, strategically situated to receive sensory input from the parietal, temporal, and occipital cortex, and is central to a well-integrated body schema. This study then suggests that depersonalization may be related to disruptions in functioning along hierarchical sensory association areas, unimodal and cross-modal, for the processing of incoming perceptions against preexisting brain templates. Also, It has been proposed that the experience of “body alienation” is associated with parietal dysfunction and that the inferior parietal lobule (BA39 and 40) is the “seat” of out-of-body experiences
Ch. 22 Dell
Disruptions in sensory association and disruptions of frontal inhibition of limbic structures might be respectively associated with which symptoms?
Disruptions in sensory cortex associative functioning may mediate the perceptual disturbances (somatosensory, visual, auditory) and sense of “unfamiliarity” characteristic of DPD. Frontal inhibition of limbic structures may mediate the hypoemotionality characteristic of DPD.
