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This is technically a disconnective effect; I'd prefer it to be under that heading --Graham (talk) 01:28, 5 February 2019 (CET)


Neurological Analysis

Various neurobiological correlates

"Like researchers quoted above, we endorse the view that depersonalization is a “hard wired” vestigial response for dealing with extreme anxiety combining a state of increased alertness with a profound inhibition of the emotional response system."

"In addition to its function as an emotional executive, the medial prefrontal cortex is also thought to be the seat of an emotion-working memory system that plays an important role in the conscious experience of emotions (Reiman et al 1997) (...) We propose that in depersonalization the above inhibitory mechanism (on the amygdala and possibly other structures of the emotional system) leads to a state of hypoemotionality and disables the process by means of which perception and cognition become emotionally colored. The latter will result in a “qualitative change” in the experiencing of perception and cognition, which is then reported by the subject as “unreal or detached”. One possibility is that these feelings of reduced emotional coloring are partially mediated (a` la James-Lange) by the marked reduction in autonomic output seen in depersonalization. Thus, there is evidence that emotional feelings are, at least partially, determined by awareness of the body changes brought about by emotional responses (LeDoux 1996; Damasio 1994). In nonemotional contexts (as occurs in the spontaneous onset of depersonalization), the same inhibitory mechanism will dampen the constant flow of body signals (i.e., body “background feelings”) that are thought to contribute to the experience of the self (Damasio 1994; Tye 1995). Such a reduction will lead to feelings of “not being there, or the feeling as if one didn’t have a body.”

"The “epilepsy model” of depersonalization has lingered on to the present day. For example, Locatelli et al (1993) reported temporal lobe electroencephalographic abnormalities in panic disorder patients with depersonalization as compared with those with panic disorder without depersonalization. In particular, patients with depersonalization showed increased slow activity and bilateral lack of fast alpha frequency response to odor stimulation. The validity of this finding is uncertain, however, as the same researchers were unable to replicate it (Locatelli et al 1995). In a single case study of a patient with ongoing depersonalization, Hollander et al (1992) reported theta activity and increased evoked potential negativities in left temporal areas suggesting temporal lobe dysfunction. Clinical associations have been reported between depersonalization and phenomena ordinarily related to the temporal lobes."

"From what has been said so far, it would seem that knowledge about the neurobiology of emotions may be an important element in the understanding of depersonalization. In this regard, converging evidence suggests that the amygdala, anterior cingulate, and medial prefrontal cortex are salient components of a parallel distributed network that integrates emotional responses (LeDoux 1994; Devinsky et al 1995). Indeed, converging evidence suggests that the amygdala plays a crucial role in assigning emotional significance to stimuli (Davis 1992; LeDoux 1992); this would not only determine type of emotional response but also “color” perceptual and cognitive experiences."

"Right or bilateral basal occipitotemporal lesions may also render patients incapable of experiencing feelings in response to visual stimuli. It has been proposed that such lesions disrupt the inferior longitudinal fasciculus, thereby disconnecting the visual association cortex (Broadmann areas 18 and 19) from temporal limbic structures. As expected, narratives by these patients are redolent of those uttered by some depersonalized subjects"

"Also supporting the analogy of depersonalization with corticolimbic disconnections is the finding that feelings of unreality may be modality specific (Sierra and Berrios 1997), and the observation has been made that the visual modality is the most frequently affected (Mayer-Gross 1935; Schilder 1935). Mayer-Gross (1935) reported patients who “only derealized as to sight”, one noting that upon closing his eyes the experience of unreality disappeared: “If I close my eyes the world seems beautiful [again] and I am quite happy” (p 111). This latter feature suggests that the putative disconnection occurs at an early stage of emotional processing, i.e., at a stage at which the different modalities are still segregated. Since the amygdala is known to receive polymodal sensory input (Amaral 1992), it might be possible to predict that the disconnection should be between inferior temporal lobes and amygdala rather than between amygdala and other limbic structures (e.g., anterior cingulate). The same view can be held in regard to the Capgras phenomenon, where the delusion is often only maintained in the visual modality (Hirstein and Ramachandran 1997)."

Mind emptiness is explored. Good figure in this paper

Additional neurobiology

"Depersonalization can be induced in subjects not suffering from the disorder by means of a pharmacological challenge with tetrahydrocannabinol (THC) (3) or the partial serotonin agonist m-CPP (4). Attempts at localizing depersonalization, although not in depersonalization disorder per se (5–12), have yielded contradictory results regarding activation, laterality, and regional involvement."

"Some lines of evidence are consistent with this temporal lobe hypothesis of depersonalization. The epilepsy literature describes depersonalization with seizures. In a series of 32 cases, 11 manifested depersonalization, four with a left-sided focus, three with a right-sided focus, and four with general dysrhythmia (5). In another series of 71 epileptic patients in whom dissociative symptoms were quantified, depersonalization was most commonly induced by partial complex seizures, more so with left-sided foci,"

"The temporal lobe was subdivided into medial and lateral regions, each with five Brodmann’s areas. There was a significant group-by-hemisphere-by-region interaction and a significant group-by-hemisphere-by-region-byBrodmann’s area interaction (Table 2). Post hoc comparisons revealed that the depersonalization disorder group had significantly lower metabolic rates in area 22 of the right superior temporal gyrus (subjects with depersonalization disorder: mean=1.06, SD=0.06; healthy comparison subjects: mean=1.11, SD=0.06; t=2.24, df=30, p<0.05) and in area 21 of the middle temporal gyrus (subjects with depersonalization disorder: "

"The main findings of this first (to our knowledge) functional imaging study of depersonalization disorder point to metabolic abnormalities primarily in the posterior cortex. Subjects with depersonalization disorder differed in relative glucose metabolic rate from comparison subjects in portions of the sensory cortex in the temporal, parietal, and occipital lobes. These specifically included right temporal area 22 (auditory association area), parietal areas 7B (somatosensory association area) and 39 (multimodal association area), and left occipital area 19 (visual association area). Depersonalization disorder subjects were characterized by greater activity than comparison subjects in all these areas, with the exception of area 22, where activity was lower. Analyses of the relative glucose metabolic rate in whole brain sensory cortex confirmed an extensive pattern of significant between-group differences.

These data do not support the primacy of temporal lobe phenomena in depersonalization, described in the introduction (5, 6, 13, 14), but rather, they implicate more extensive associational brain networks, given the prominent occipital and parietal findings. The perceptual alterations that are hallmark symptoms of depersonalization primarily involve two sensory modalities, visual and somatosensory, although auditory disturbances can also be described. There is a hierarchy of sensory processing in the brain, from primary sensory areas to unimodal and then polymodal association areas and finally to the prefrontal cortex (27). Unimodal association areas showed more activity in depersonalization disorder subjects, both in occipital area 19 of the prestriate visual cortex and parietal area 7B, which is believed to be central to high-order integration within the somatosensory system (28). Dissociation and depersonalization scores showed a strong positive correlation with area 7B activity. Multimodal sensory integration occurs in the region of the parietal-temporal-occipital junction or the inferior parietal lobule (27, 29). Area 39, which corresponds to the angular gyrus and is implicated in somatosensory-visual-auditory integration, was again more active in depersonalization disorder subjects"[1]

Good figure in this paper (good neurology paper in general)

Additional-er neurobiology

"Circuits likely to mediate symptoms of depersonalization are hypothesized to include'cortical areas involved in integration of sensory and somatic processing. Certainly, lesions in temporal-parietal regions may result in hypoemotionality and out-of-body experiences.1318 An early positron emission tomography study found altered metabolic activity in temporal-parietal occiptal regions involved in integration of sensory processing and of the body schema (Figure 1).19 Depersonalization symptoms have been related to increased volumes of superior parietal cortices in personality disorder.20

Circuits likely to mediate emotional and cognitive disruption in DPD might be hypothesized to include prefrontal and limbic regions involved in cognitive-emotional regulation. Indeed, functional magnetic resonance imaging studies of DPD have demonstrated decreases (rather than the usual increases) in activity in regions involved in affective processing (eg, amygdala, insula) (Figure 2).6,21-23 In addition, there may be increased recruitment of (inhibitory) prefrontal regions to emotionally salient stimuli.21-22

The precise way in which these various neurocircuits account for depersonalization symptoms remains to be fully understood.24,25 It is notable, however, that disruptions of prefrontal-limbic interactions are also seen in other disorders where dissociative mechanisms may play a role, including posttraumatic stress disorder and the functional somatic disorders (where there may be hypoactivation of prefrontal structures and hyperactivation of limbic structures).26 Various emotional regulation and hypnosis paradigms may be useful in further exploring the relevant mechanisms.27,28

Neurotransmitters in circuitry that mediates depersonalization include the serotonin, glutamate, and opioid systems.2


DPD is accompanied by autonomic blunting,36,37 likely mediated by a range of molecular systems including the noradrenergic system and components of the hypothalamic-pituitary-adrenal axis (HPA). Indeed, DPD is characterized by lower basal levels of norepinephrine,38 and evidence of diminished HPA axis sensitivity.39,40"[2]

Depersonalization may be a form of emotion processing disorder

"Healthy volunteers and OCD patients, but not the depersonalized patients, activated the insula in response to the aversive scenes, and statistical contrasts between the depersonalized patients and the other groups were significant. This brain region has been implicated previously in the neural response to disgust (Phillips et al., 1997), other negative moods (Reiman et al., 1997; Mayberg et al., 1999) and unpleasant visceral sensations such as pain (Ploghaus et al., 1999). Paradoxically, this area was activated in the depersonalized patients, and to a significantly greater extent compared with normal control subjects, when they were shown neutral scenes. Regions important for visual object and spatial perception middle and superior temporal gyri, and the inferior parietal lobe were also activated to a significantly greater extent in normal control subjects and OCD patients compared with depersonalized patients when they viewed the aversive scenes. These findings are similar to those of a previous study, in which depersonalized patients demonstrated reduced metabolism within middle and superior temporal gyri during performance of a variant of the California Verbal Learning Test (Simeon et al., 2000). Activation of occipito-temporal cortex has been demonstrated in the response to expressions of fear and disgust (Morris et al., 1996; Phillips et al., 1997), and to the same unpleasant scenes we used (Lane et al., 1997; Lang et al.,1998). The increased activation in these regions in both normal control subjects and OCD patients, in particular, middle and superior temporal gyri, may reflect the heightened visual attention and processing induced by aversive stimuli in these subjects but not the depersonalized patients. The normal control subjects also demonstrated significantly greater activation in bilateral anterior cingulate gyri and the left posterior cingulate gyrus in response to the aversive scenes compared with the depersonalized patients. These areas have been previously associated with the experience of negative mood (Mayberg et al., 1999) and emotional appraisal (Maddock, 1999), respectively."[3]

Skin conductive response measured emotional differences in response to stimuli

"our findings support the view that depersonalization disorder is characterized by reduced emotional reactivity to emotional stimuli"[4]

Sensory integration dysfunction promotes feelings of unreality, with anxiety affecting some of these functions

"Our earlier studies also showed different unreal perceptions of self-motion, perceived unequally by the different parts of the body [8]; moreover, we discovered vestibularly evoked visual hallucinations [9]. All this indicates the multisensory effects of vestibular stimulation. Sang et al. have established that patients with peripheral vestibular disease often report symptoms of Dp/Dr [10]. They proposed that derealization occurs in these patients because their distorted vestibular signals create a misleading frame of spatial reference, which does not match with the other senses, giving rise to illusory, “unreal” perceptions of the patient's transactions in the physical world. During the acute phase of a unilateral peripheral vestibular lesion the poor spatial orientation of vestibular patients cooccurs with Dp/Dr symptoms, including attention/concentration difficulties and somatic depression symptoms. Months later Dp/Dr symptoms in these patients decrease, but somatic symptoms of depression persist [11]. In addition, those vestibular patients who have an acquired deficiency of other special senses, for example, vision and hearing, also have more frequent and severe Dp/Dr symptoms than do healthy controls. These symptoms are always associated with symptoms of common mental disorders [12]."

"Sensory integration of vestibular information, vision and proprioception fails to occur because the deranged information from the vestibular system does not match with the other sensory inputs and expectations learned by past experience. All these symptoms were evidence for Dp/Dr. We argue that vestibular dysfunction increases Dp/Dr symptomatology by distorting perception [10–12, 30]. The present study revealed that anxiety does not consistently influence these symptoms. In other words, the mechanism of their generation is not essentially related to the anxiety. Therefore, we can assume that anxiety is involved in the generation of some of the Dp/Dr symptoms but not of all."

"Symptoms like “feeling as though in a dream,” “feeling of detachment or separation from surroundings,” and “feeling detached or separated from body” have been reported before as evidence for derealization due to the failure of the sensory integration. They occur most frequently and best distinguish patients with vestibular disorders from healthy subjects [10–12, 30]. However, interestingly, we did not find any significant difference in the reports of these symptoms made by healthy subjects and vestibular patients without anxiety (Table 3). Quite the contrary, these symptoms distinguish the vestibular patient group with anxiety from both the vestibular patients without anxiety and from healthy subjects. Another group of symptoms such as “body feels numb,” “numbing of emotions,” “thoughts seem blurred,” “events seem to happen in slow motion,” “your emotions seem disconnected from yourself,” “feel as though in a trance,” “feel confused or bewildered,” and “feel isolated from the world” also indicate a difference between vestibular patients with anxiety and the other two groups studied. The frequency and severity of all these Dp/Dr symptoms apparently are influenced by the presence of anxiety in the vestibular patients."[5]

DP correlates with burning out of a medical profession

"This study confirms the ability of two single item measures of emotional exhaustion and depersonalization to provide important information on the likelihood of high burnout among physicians and medical students."

"This study’s main strength is its large sample size, inclusion of participants from a variety of practice settings including national samples of physicians and medical students, and the striking consistency of the results across samples. Our aggregate sample of 10,525 physicians and medical students compares favorably with the original MBI validation sample of 1,104 physicians and nurses."[6]

Acute stress/trauma triggers this effect in a certain way + pharmacotherapy notes

"Stress, trauma, and the neurobiology of dissociation. Acute trauma responses to motor vehicle accidents, various forms of abuse, and imprisonment include depersonalization and derealization.2 These responses, in themselves, are not necessarily unusual or “abnormal” in certain acute situations. Several researchers have proposed that depersonalization is an inhibitory response that is “hard-wired” to diminish anxiety and foster hyperarousal states.3,12 Under these conditions, the person transforms into a survival mode where physical resources are conserved and adaptive behavior takes control during the threatening or dangerous situation. The individual’s response becomes pathological when the response either generalizes to other situations or persists beyond the immediate threat.

Spiegel et al3 outlines the consistently documented threefold neurobiological patterns found in DDD: 1) activation in posterior cortical sensory association areas (especially inferior parietal lobule); 2) prefrontal activation, and 3) limbic inhibition. These alterations are consistent with simulated “out of body” experiences involving the inferior parietal lobule.3 Patients with DDD also have a distinct pattern of dysregulation of the hypothalamic-pituitary-adrenal axis.3 Specifically, in DDD, the following are seen: 1) baseline hyperactivity, 2) diminished negative feedback inhibition, and 3) blunted reactivity to psychosocial stress. Other neurobiological changes specific to DDD reported by Simeon et al14 include marked decline of basal norepinephrine in response to anxiety co-occurring with increase in noradrenergic tone. Overall, there is evidence for the hypothesis that autonomic blunting occurs in DDD.3,14"

"There is no known pharmacotherapy for the treatment of DDD.13 The literature includes trials of clomipramine, selective serotonin reuptake inhibitors, and lamotrigine.12,13 Research using selective serotonin reuptake inhibitors in patients with DDD has shown that serotonin agonists such as meta-chlorphenylpiperazine can induce symptoms of depersonalization and/or derealization1. Sierra12 suggested possible agents may include opioid agonists, N-methyl-D-aspartate (NMDA) agonists, and serotonin 2C agonists. No efficacy for any of these medications or classes was proven. More research is needed as the evidence is inconclusive.

Atypical (or second generation) antipsychotic drugs that block both dopamine (D2) and serotonin (5HT2A) receptors may be of use in treating complex trauma cases with “psychotic features” although the psychiatrist should carefully evaluate symptoms that appear to be abnormal perceptions taking into account the dissociative symptoms reported by the patient. Opioid antagonists have also shown some promise in the treatment of dissociative symptoms;1 the mu and kappa systems in particular have been implicated in symptoms of depersonalization and analgesia. Naltrexone, an opioid antagonist, has exhibited some effect in reducing symptoms of DDD.1,13,14"[7]

DP has been proposed as a defence mechanism for anxiety although there are some fundamental differences + neural correlates + emotional processing dysfunction + sensory integration dysfunction

"Depersonalization has been shown to correlate with anxiety measures (Trueman, 1984), and patients with a diagnosis of DPD, a condition characterised by chronic depersonalization are often found to have high levels of anxiety (Baker et al., 2003). Additionally, it has been observed that the onset of depersonalization often coincides with stressing life-events or even life threatening situations. This has been interpreted as suggesting that depersonalization represents an anxiety triggered ‘hard wired’ inhibitory response intended to ensure the preservation of adaptative behaviour during situations normally associated with overwhelming and potentially disorganizing anxiety (Sierra & Berrios, 1998). It has been proposed that such inhibitory response is mediated by a fronto-limbic suppressive mechanism, which would generate a state of emotional numbing, and disable the process by means of which perception (including that of one’s own body), as well as cognition become emotionally coloured. Such ‘decolouring’ will result in a ‘‘qualitative change’’ of conscious awareness, which is then reported by the subject as ‘‘unreal or detached’’. In patients with DPD this response would become abnormally persistent and dysfunctional (Sierra & Berrios, 1998). Studies carried out during the last decade seem supportive of this model."

"the highest basal autonomic activity was observed in the chronic anxiety group (almost four times higher than observed in the depersonalization group), both groups had similarly high subjective anxiety. The authors concluded: ‘‘The evidence suggests that the discrepancy between subjective and objective signs of anxiety is the fundamental characteristic of patients with depersonalization. In physiological terms, anxiety is experienced but is not translated into defence reaction arousal’’ (Kelly & Walter, 1968)."

"These findings suggested the presence of both inhibitory and facilitatory mechanisms on autonomic arousal, which suggests a specific disruption in emotion processing rather than a non-specific dampening effect on autonomic reactivity."

"Interestingly, one of the most significant findings was that of an abnormally increased activation in the angular gyrus of the right parietal lobe, which correlated (r = 0.7) with ratings of depersonalization intensity. The potential significance of abnormal parietal functioning in depersonalization is further suggested by a recent open label trial using low frequency repetitive transcranial magnetic stimulation (TMS) on the right temporoparietal junction in 12 patients with DPD (Mantovani et al., 2010). It was found that after 3 weeks treatment half of the patients showed significant improvement"

"Experimental neuroimaging studies on the neural correlates of embodiment and agency feelings, have identified a network of parietal regions, which appear to play an important role in the generation of embodiment and agency feelings: the inferior parietal cortex, the temporoparietal junction, and the posterior insula. Increased activation in the angular gyrus has been observed in patients experiencing a lack of agency feelings regarding movement or the experience that movements are being controlled by an external agency (Farrer et al., 2004; Frith, Blakemore, & Wolpert, 2000)."


DP with anxiety comorbidity presents higher responses towards disgust, whereas DP w/o anxiety does not

"The main finding of the study is that patients in the anxiety group were found to have heightened autonomic responses to disgust expressions as compared with DPD patients and normal controls. Most interesting however, is the finding that patients with depersonalization did not show this autonomic hyperreactivity, in spite of the fact that both the DPD and anxiety groups reported similar levels of subjective anxiety as measured by the anxiety scales. Indeed, in view of the high anxiety levels in the DPD patients, it is striking that their autonomic responses to disgust resembled those of the non-anxious controls. This finding would seem to suggest that the presence of depersonalization in otherwise anxious patients has a blunting effect on autonomic reactivity. The fact that we found a negative correlation trend between scores on the CDS and SCRs to disgust expressions would seem consistent with this view. As mentioned above, our findings are in agreement with a recent study comparing levels of urinary norepinephrine in patients with depersonalization disorder and normal controls. Although depersonalization accompanied by anxiety was associated with increased noradrenergic tone as compared with normal controls, within the depersonalization group there was a marked basal norepinephrine decline with increasing levels of depersonalization (Simeon et al., 2003b). Similarly, Delahanty et al. (2003) found that amongst survivors of motor vehicle accidents, 15-h urinary norepinephrine was inversely correlated to the severity of peritraumatic dissociation."[9]

DP presents increased vulnerability towards distractibility

"Very much in line with our previous study (Guralnik et al., 2000), the DPD group had intact general intelligence, but demonstrated subtle impairments in short-term memory. The current findings show that manifest longterm memory deficits are subsidiary to difficulties in earlier stages of information processing. Moreover, we found no group differences on the working memory index of the WAIS, as well as on the PASAT, rendering it unlikely that the cognitive disruption in DPD rests within the domain of working memory. Therefore, considering our present and previous findings (Guralnik et al., 2000), we suspect that compromises in short-term memory might be attributable to even earlier stages of information processing (i.e., perception and attention). In fact, the DPD group showed a trend towards significant impairment on the WAIS Perceptual Organization index, as well as an overall reduced processing speed on the respective WAIS index, all suggestive of difficulties in readiness to efficiently process new perceptual information. Further supporting this viewpoint, dissociation severity was associated with difficulty focusing attention and vulnerability to distraction. Moreover, dissociation severity, as measured by the DES total but not depersonalization symptoms, was related to lower total IQ scores. This is finding is in line with studies showing that higher DES scores but not depersonalization symptoms go along with subtle deficits in executive functioning (Cima et al., 2001; Giesbrecht et al., 2004)."[10]

The opioid system plays a role in the psychopathology of this disorder

"The opioid system seems to play an insignificant role in the pathogenesis of the endogeneous depression (Banki and Araio, 1987). As mentioned above, we used indirect data which suggested the importance of the opioid system in the pathogeneses of depersonalization, i.e. some depersonalization symptoms resemble the effect of morphine and depersonalization arises as a reaction to an acute emotional stress, which causes endorphin secretion.

The positive therapeutic effect of the opioid receptor blocker, naloxone, offers some evidence for the implication of the opioid system in the pathogenesis of depersonalization. This role is also confirmed by the influence of naloxone on the cortisol secretion in depersonalization patients: the low level of cortisol in depersonalization patients could be explained by the fact that endogeneous opioids inhibit CRF secretion. By blocking the action of endorphins, naloxone increases the cortisol secretion (Delitala et al., 1994). The depersonalization patients were found to have a much lower cortisol content in plasma, which was drastically increased by naloxone. The increase of cortisol level coincided in time with the therapeutic effect of naloxone. There was a reduction of depersonalization symptoms without any signs of anxiety.

Our data do not provide sufficient evidence to conclude whether the therapeutic effect of naloxone is only related to the blockade of the opioid receptors or to some other factors that affect the opioid system. In most patients, the positive action of naloxone developed during the first hours after the infusion and, in many, the improvement lasted more than 24 h. Because the half-life of naloxone is approximately 60 min, this suggests that naloxone increased the patients’ therapeutic sensitivity to the drugs that were previously not very effective for these particular patients"[11]

Marijuana intoxication induces this effect with no experience of anxiety or dysphoric mood

"The physiological basis for anxiety and euphoria is believed to be increased levels of brain arousal (4648). Arousal refers to levels of generalized, diffuse activation of the brain mediated by the brain stem reticular activating system (49-51). The frontal lobe is believed to be the cortical representative of the arousal chain (52). Evidence from a variety of sources indicates that frontal blood flow may also be sensitive to levels of brain activation (53). Several lines of evidence support a THCinduced increase in brain activation. After marijuana smoking, the EEG shifts in favour of fast frequencies, especially over the frontal lobes (54, 55). After marijuana intoxication, cerebral blood flow shows a diffuse increase, especially over the frontal lobes (56). Although marijuana use increases brain arousal, the associated mood change is not one of dysphoria, but of euphoria. Excitement, although associated with increased brain arousal, is not always unpleasant. In the present study, post-THC increases in CBF were observed all over the cortex. However, the changes were most marked over the frontal lobes. As expected, marijuana intoxication correlated positively with most regional CBFs. When level of intoxication was included in the model, depersonalization showed a positive correlation with most brain regions, which reached the level of significance in two of them. This would support the notion that depersonalization is a mechanism triggered by increased activation levels."

"The mechanism of dissociation associated with depersonalization may, indeed, be related to malfunction of the anterior cingulate. According to Papez, the cingulate gyrus is the ‘seat of dynamic vigilance by which emotional experiences are endowed with an emotional consciousness.’ This brain region, which is transposed between the subcortical and cortical structures, may be responsible for integrating the subcortical and cortical mechanisms which contribute to the composite feeling of self."[12]

There was a very strong association between increasing dissociation severity and declining norepinephrine

"Norepinephrine plays a central role in arousal, attention and emotional memory. In PTSD, basal catecholamine, noradrenergic challenge and receptor binding studies have revealed heightened noradrenergic tone, consistent with the hyperarousal and intrusive symptomatology characteristic of the disorder (Southwick et al., 1999). In contrast, given the ‘shut-down’ symptomatology typically characteristic of dissociative states, one might predict autonomic hyporesponsivity"

"Within the dissociative group there was a very strong association between increasing dissociation severity and declining norepinephrine, independent of anxiety; indeed dissociation and anxiety were not intercorrelated. We speculate that this noradrenergic blunting might partly explain the hypoarousal, attentional difficulties and short-term memory deficits characteristic of depersonalization (Guralnik et al., 2000). Our finding is in good accordance with other reports describing autonomic physiologic blunting in dissociation (Griffin et al., 1997; Sierra et al., 2002). The present finding is also very similar to the single published study, to our knowledge, which has examined norepinephrine and dissociation (Delahanty et al., 2003). This study found that in the immediate aftermath of motor vehicle accidents, 15-h urinary norepinephrine was inversely correlated to the severity of peritraumatic dissociation."[13]

DP may be due to glutamate receptor imbalance

"Glutamate release in prefrontal cortex is increased by subanaesthetic doses of ketamine, while anaesthetic doses decrease the glutamate release [7]. This may be due to the relative sensitivity of GABAerg compared to glutamaterg neurons regarding NMDA antagonism, thus resulting in reduced GABAerg inhibition in lowdose ketamine administration [13]. Resulting increased activity in prefrontal glutamaterg neurons supposedly inhibits, possibly via intercalated GABAerg cells, projection from centromedial and basolateral nuclei in amygdala [14,15], thus, affecting structures critically involved in depersonalization [16]. However, the changes in glutamate release may have different functional effect in the present of ketamine – blocking postsynaptic NMDA receptors, compared to ketamine naïve depersonalization states (i.e. depersonalization disorder). Possibly, in depersonalization disorder there is an inherent low NMDA receptor sensitivity or a high amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor sensitivity resulting in a receptor activation imbalance mimicked by low-dose ketamine administration. But while the ketamine-induced imbalance is driven by the increased glutamate release, the inherent imbalance in depersonalization disorder is present regardless if prefrontal glutamate release is normal (i.e. during lamotrigine treatment) or high."[14]

Dexamethasone, a steroid agonist of the glucocorticoid receptor, suppressed cortisol more in DP patients

"Thus, dissociation may involve a pattern of HPA axis dysregulation which differs from PTSD. The current study suggests that dissociation may be associated with normal or elevated baseline cortisol and diminished negative feedback, while PTSD is associated with reduced baseline cortisol and enhanced negative feedback (Yehuda 1997)."[15]

Lamotrigine is not effective a sole treatment for DP in modulating glutamate

" A double-blind, placebo-controlled, cross-over design was used to evaluate 12 weeks of treatment of lamotrigine. Subjects comprised nine patients with DSM-IV depersonalization disorder. Changes on the Cambridge Depersonalization Scale and the Present State Examination depersonalization/derealization items were compared across the two cross-over periods. Lamotrigine was not significantly superior to placebo. None of the nine patients was deemed a responder to the lamotrigine arm of the cross-over. Lamotrigine does not seem to be useful as a sole medication in the treatment of depersonalization disorder."[16]

DP and childhood trauma are inversely related with mindfulness

"In confirmation of our hypothesis, we found a strong negative relationship between DP severity and mindfulness. This pronounced connection between CDS-9 and MAAS is explained significantly by strong correlations with MAAS items concerning being on “autopilot,” which account for almost 40% of the variance of DP severity."

"With respect to the relevance of childhood adversities, we found a significant association between DP severity and emotional abuse and neglect in the nonpatients. This result is in line with findings from a mixed sample of patients with DP disorder and healthy controls, where emotional abuse was found to be specifically related to DP severity (Simeon et al., 2001). In this context, it is interesting that we also found a strong inverse correlation between emotional abuse/neglect during childhood and mindfulness in the nonpatient sample."[17]

No evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma.

"Patients with depersonalization/derealization during panic attacks did not report significantly more childhood trauma events than patients without such symptoms (table 1). In fact, the only significant finding was in the opposite direction: patients who reported having been punished with an object that produced bruises or bleeding were significantly less likely to experience depersonalization/derealization during panic attacks than patients who had not been harshly punished (table 1). This result may be a chance finding due to multiple comparisons. Similar results were found in the two analyses when the group was divided into groups with high and low levels of trauma. Patients with high levels of trauma—those who reported more than two or three different childhood traumatic events—were less likely to report depersonalization/derealization during panic than the remainder of the group (χ2=4.33, df=1, p=0.04, N=74, and χ2=6.86, df=1, p=0.009, N=74, respectively). Findings also did not differ when only those with severe depersonalization/derealization were compared to those without such symptoms."[18]

Comorbidity with DR reported @ 80%

"To index the overlap between dissociative symptoms, we calculated the percentage of participants reporting each dissociative symptom who also reported another dissociative symptom. Table 2 indicates that derealization was reported by the majority of participants who reported numbing (79%). reduced awareness (85%), and depersonalization (80%)."[19]

Good fMRI review paper

Brain Activation during Script-Driven Imagery Induced Dissociative Responses in PTSD: A Functional Magnetic Resonance Imaging Investigation

Good pharmacological approach to treating DP paper

Depersonalization disorder: pharmacological approaches


  1. Simeon, D., Guralnik, O., Hazlett, E. A., Spiegel-Cohen, J., Hollander, E., & Buchsbaum, M. S. (2000). Feeling unreal: a PET study of depersonalization disorder. American Journal of Psychiatry, 157(11), 1782-1788.
  2. Stein, D. J., & Simeon, D. (2009). Cognitive-affective neuroscience of depersonalization. CNS spectrums, 14(9), 467-471.
  3. Phillips, M. L., Medford, N., Senior, C., Bullmore, E. T., Suckling, J., Brammer, M. J., ... & David, A. S. (2001). Depersonalization disorder: thinking without feeling. Psychiatry Research: Neuroimaging, 108(3), 145-160.
  4. Sierra, M., Senior, C., Dalton, J., McDonough, M., Bond, A., Phillips, M. L., ... & David, A. S. (2002). Autonomic response in depersonalization disorder. Archives of General Psychiatry, 59(9), 833-838.
  5. Kolev, O. I., Georgieva-Zhostova, S. O., & Berthoz, A. (2014). Anxiety changes depersonalization and derealization symptoms in vestibular patients. Behavioural Neurology, 2014.
  6. West, C. P., Dyrbye, L. N., Sloan, J. A., & Shanafelt, T. D. (2009). Single item measures of emotional exhaustion and depersonalization are useful for assessing burnout in medical professionals. Journal of general internal medicine, 24(12), 1318.
  7. Gentile, J. P., Snyder, M., & Gillig, P. M. (2014). STRESS AND TRAUMA: psychotherapy and pharmacotherapy for depersonalization/derealization disorder. Innovations in clinical neuroscience, 11(7-8), 37.
  8. Sierra, M., & David, A. S. (2011). Depersonalization: a selective impairment of self-awareness. Consciousness and cognition, 20(1), 99-108.
  9. Sierra, M., Senior, C., Phillips, M. L., & David, A. S. (2006). Autonomic response in the perception of disgust and happiness in depersonalization disorder. Psychiatry research, 145(2-3), 225-231.
  10. Guralnik, O., Giesbrecht, T., Knutelska, M., Sirroff, B., & Simeon, D. (2007). Cognitive functioning in depersonalization disorder. The Journal of nervous and mental disease, 195(12), 983-988.
  11. Nuller, Y. L., Morozova, M. G., Kushnir, O. N., & Hamper, N. (2001). Effect of naloxone therapy on depersonalization: a pilot study. Journal of Psychopharmacology, 15(2), 93-95.
  12. Mathew, R. J., Wilson, W. H., Chiu, N. Y., Turkington, T. G., DeGrado, T. R., & Coleman, R. E. (1999). Regional cerebral blood flow and depersonalization after tetrahydrocannabinol adrninistration. Acta Psychiatrica Scandinavica, 100(1), 67-75.
  13. Simeon, D., Guralnik, O., Knutelska, M., Yehuda, R., & Schmeidler, J. (2003). Basal norepinephrine in depersonalization disorder. Psychiatry Research, 121(1), 93-97.
  14. Pikwer, A. (2011). Depersonalization disorder may be related to glutamate receptor activation imbalance. Medical hypotheses, 77(4), 593-594.
  15. Simeon, D., Guralnik, O., Knutelska, M., Hollander, E., & Schmeidler, J. (2001). Hypothalamic-pituitary-adrenal axis dysregulation in depersonalization disorder. Neuropsychopharmacology, 25(5), 793.
  16. Sierra, M., Phillips, M. L., Ivin, G., Krystal, J., & David, A. S. (2003). A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder. Journal of Psychopharmacology, 17(1), 103-105.
  17. Michal, M., Beutel, M. E., Jordan, J., Zimmermann, M., Wolters, S., & Heidenreich, T. (2007). Depersonalization, mindfulness, and childhood trauma. The Journal of nervous and mental disease, 195(8), 693-696.
  18. Marshall, R. D., Schneier, F. R., Lin, S. H., Simpson, H. B., Vermes, D., & Liebowitz, M. (2000). Childhood trauma and dissociative symptoms in panic disorder. American Journal of Psychiatry, 157(3), 451-453.
  19. Harvey, A. G., & Bryant, R. A. (1999). Dissociative symptoms in acute stress disorder. Journal of traumatic stress, 12(4), 673-680.