the neuroscience of depersonalization

Depersonalization: A New Look at a Neglected Syndrome is very comprehensive without being very long. The topic is “neglected” because it’s nearly as common as depression and anxiety, in both normal and psychiatrically diagnosed populations, but people don’t seem to talk about it much. Perhaps because it’s an experience of ineffable strangeness. It was recognized a long time ago, though.

Griesinger, 1845:

We sometimes hear the insane, especially melancholics, complain of a quite different kind of anaesthesia…I see, I hear, I feel, they say but the object does not reach me; I cannot receive the sensation; It seems to me as if there was a wall between me and the external world.

Billod, 1847:

she claimed to feel as if she were not dead or alive, as if living in a continuous dream…objects [in her environment] looked as if surrounded by a cloud; people seemed to move like shadows, and words seemed to come from a far away world.

They report on a factor analysis of the Dissociative Experiences Scale and use it to organize some of the discussion. The factors:

  1. Anomalous body experience..

    I see my hands and my body doing things but it does not feel like me and I am not connected to it at all. I don’t feel alive in any way whatsoever. I don’t feel a thing except for hot or cold; maybe hunger. Even if I touch my face I feel or sense something but my face is not there. As I sense it I have the need to make sure and I rub, touch, or hurt myself to feel something.

    as I walked I had the distinct feeling of being floating or bouncing up and down on a rubber floor, I wanted to avoid a group of people as I realised they might make fun of my walking. To my surprise they did not seem to have noticed a thing.

  2. Emotional numbing.

    I seem to be walking about in a world I recognise but don’t feel.

    There are two interesting clinical paradoxes regarding the experience of emotional numbing. The first is that, in spite of their subjective complaints, depersonalized patients show a normal array of emotional motor expressions. In fact, to an external observer they can come across as emotional individuals…The second paradox is the coexistence of complaints of pervasive emotional numbing with those of intense distress and suffering…As a matter of fact, however, the very absence of feelings is frequently identified by patients as their major source of distress.

  3. Anomalous subjective recall.

    I can remember things, but it seems as if what I remember did not really happen to me.

    It seems as if things that I have recently done had taken place a long time ago. For example, anything which I have done this morning feels as if it were done weeks ago.

    Another common clinical observation is that autobiographic memories in depersonalization are usually remembered from a vantage point outside of the body…This type of memory distortion…has been shown to affect the recall of traumatic situations, or situations which were experienced as threatening…It was found that highly avoidant individuals were more likely to remember their trauma from an observer perspective than individuals with a lower level of avoidance. Interestingly, avoidance did not influence the vantage point for positive or neutral memories. The results support the view that the adoption of the observer vantage point for unpleasant memories may serve a distancing, defensive function for people affected by trauma. Similar results have been reported in regards to distressing memories in depression, and memories related to social interactions in social phobics.

    patients also complain of feelings of mind emptiness, as if they did not have any thoughts. Such experiences are redolent of absorptive states. Interestingly, in the factor analysis mentioned above, it was found that the factor “anomalous subjective recall” correlated significantly with the absorption subscale on the Dissociative Experiences Scale…Patients with depersonalization are often self-absorbed and experience a form of compulsive self-scrutiny, which could affect subjective recall, imagery, and time experiencing.

  4. Alienation from surroundings/derealization.

    Clinical observations suggest that an inability to experience the hedonic attributes of things perceived is an important feature of depersonalization…in the factor analysis described above, an item describing a form of anhedonia loaded on this factor rather than on the emotional numbing factor.

“Redolent of absorptive states” indeed. It seems important that a minority of people who experience depersonalization find it pleasant or neutral. Indeed, death of the ego is a frequently-mentioned reason for using hallucinogens. “Compulsive self-scrutiny” would be a non-charitable way of describing the ideal meditation practice: one that’s continuous with daily life. Meditating Selflessly has more data and speculation surrounding this topic. What seems interesting is that naming mental states is part of the instructions sometimes given for vipassana, and then there’s this:

Putting feelings into words: affect labeling disrupts amygdala activity in response to affective stimuli.

Putting feelings into words (affect labeling) has long been thought to help manage negative emotional experiences; however, the mechanisms by which affect labeling produces this benefit remain largely unknown. Recent neuroimaging studies suggest a possible neurocognitive pathway for this process, but methodological limitations of previous studies have prevented strong inferences from being drawn. A functional magnetic resonance imaging study of affect labeling was conducted to remedy these limitations. The results indicated that affect labeling, relative to other forms of encoding, diminished the response of the amygdala and other limbic regions to negative emotional images. Additionally, affect labeling produced increased activity in a single brain region, right ventrolateral prefrontal cortex (RVLPFC). Finally, RVLPFC and amygdala activity during affect labeling were inversely correlated, a relationship that was mediated by activity in medial prefrontal cortex (MPFC). These results suggest that affect labeling may diminish emotional reactivity along a pathway from RVLPFC to MPFC to the amygdala.

Top-down, prefrontal cortex-dependent suppression of emotion is an important part of depersonalization. This involves the amygdala and also the insula. Emotional significance isn’t being connected to sensory input in a normal way. The role of the insula in particular is interesting, since it’s related to bodily self-awareness, drug cravings, and mindfulness meditation. There seems to be a major convergence there. This pattern of hyper-frontality is ALSO seen in fMRI studies of drugs that cause depersonalization: ketamine, psilocybin, and cannabis. Using a “polygraph,” patients with depersonalization sweat less in response to disgusting imagery than other people (“sympathetic arousal”). The insula is notably involved in disgust, and I definitely felt dead and depersonalized when I was performing ex-sanguination followed by transcardial perfusion with formalin solution on rats. The link shows what it says, graphically.  One day, I’m sure I’ll rant about vegan stuff.  You need properly abstract language (pdf) to distance yourself from the actual gory awfulness of what you’re seeing.

Another interesting comparison is between feelings of “lack of agency” or “lack of body ownership” on the one hand, and neglect syndromes caused by parietal damage on the other. Like the insula, the parietal lobe is involved in representing the body, including propioception. Parts of the parietal lobe also contain body-centered, “ego-centric” maps of space, as opposed to the “allocentric” spatial representations in the hippocampus (a Nobel Prize-winning discovery). This is discussed in Meditating Selflessly. Something the book doesn’t mention is the role of the vestibular system in feelings of agency and body ownership and, interestingly, perspective-taking:

As mentioned earlier, perspective taking necessitates the translocation of one’s own egocentric viewpoint into a third-person, allocentric, reference. This operation requires geometrical transformations such as translations and rotations of the viewpoint. We propose that vestibular signals play an important role in these mental transformations of the viewpoint as they have been involved in several aspects of egocentric and allocentric mental imagery (Mast et al., 2006; Dilda et al., 2012)

There are more cannabinoid receptors in the cerebellum (vestibular system) and hippocampus (allocentric spatial processing) than most places.

It’s also noteworthy that opioids are heavily implicated in dissociation, while the depersonalization book notes that rates of depersonalization are higher in people with chronic pain. Pain tolerance is also higher in Zen meditators.  The latter finding doesn’t follow the same pattern as the rest:

Using functional magnetic resonance imaging and a thermal pain paradigm we show that practitioners of Zen, compared to controls, reduce activity in executive, evaluative and emotion areas during pain (prefrontal cortex, amygdala, hippocampus). Meditators with the most experience showed the largest activation reductions. Simultaneously, meditators more robustly activated primary pain processing regions (anterior cingulate cortex, thalamus, insula). Importantly, the lower pain sensitivity in meditators was strongly predicted by reductions in functional connectivity between executive and pain-related cortices. Results suggest a functional decoupling of the cognitive-evaluative and sensory-discriminative dimensions of pain, possibly allowing practitioners to view painful stimuli more neutrally. The activation pattern is remarkably consistent with the mindset described in Zen and the notion of mindfulness. Our findings contrast and challenge current concepts of pain and emotion regulation and cognitive control; commonly thought to manifest through increased activation of frontal executive areas. We suggest it is possible to self-regulate in a more ‘passive’ manner, by reducing higher-order evaluative processes, as demonstrated here by the disengagement of anterior brain systems in meditators.

When does depersonalization even happen?

Most cases of “normal depersonalization” are usually experienced during anxiety-producing situations or low mood. Other commonly accompanying states are characterized by some form of anomalous arousal (65%) such as hypnagogic states; sleep deprivation; sensory deprivation; alcohol withdrawal, and during physical illness and fatigue…Subjects frequently stated that they had recently passed through a period of effort, danger, strain, or mental concentration. However, rather than experiencing the onset of depersonalization at the peak of stress, it frequently coincided with the release of tension following the resolution of the stressful situation. Studies focusing on personality factors have found that “emotional instability” or anxiety seem to confer vulnerability to depersonalization experiences.

Maybe it’s the endorphins. Or the dynorphin. Salvinorin A is about as depersonalizing a thing as there is, and it’s a kappa agonist. Stress, pain, the amygdala, endogenous opioids. It’s a consistent story. Except for norepinephrine.

On the one hand, reducing norepinephrine-induced hyper-arousal is part of the appeal of opiates. CB1 receptors and mu opioid receptors are found in overlapping places, and there’s a deep convergence between the effects of cannabinoids and opioids.  Interestingly, caffeine may block cannabinoid-opioid synergy:

Relapse is the most serious limitation of effective medical treatment of opiate addiction. Opiate-related behaviors appear to be modulated by cannabinoid CB1 receptors (CB1) through poorly understood cross-talk mechanisms. Opiate and CB1 receptors are coexpressed in the nucleus accumbens (NAc) and dorsal striatum. These regions also have the highest density of adenosine A2a receptors (A2a) in the brain. We have been investigating the postsynaptic signaling mechanisms of mu-opiate receptors (MORs) and CB1 receptors in primary NAc/striatal neurons. In this article, we present evidence that MOR and CB1 act synergistically on cAMP/PKA signaling in NAc/striatal neurons. In addition, we find that synergy requires adenosine and A2a. Importantly, an A2a antagonist administered either directly into the NAc or indirectly by i.p. injection eliminates heroin-induced reinstatement in rats trained to self-administer heroin, a model of human craving and relapse. These findings suggest that A2a antagonists might be effective therapeutic agents in the management of abstinent heroin addicts.

Cannabinoids increase norepinephrine release, though, and one effect of mescaline is to cause the locus coeruleus to burst in response to normally-boring stimuli. This might have something to do with making things seem more alive, subjectively, rather than dead. Being on drugs is a form of “anomalous arousal,” though, and there might be something to do the idea that altered states of consciousness are just weird things that happen to the sleep/wake cycle. Drugs are often described as dream-like.

THC, psilocybin, and ketamine all produce “depersonalization,” but even rats can tell the differences among them.  The common denominator seems to be the “default mode network” (DMN) and the “task positive network” (TPN) being active simultaneously, more than usual (something similar is seen with cannabinoids):

In summary, the results of the present study strongly imply that increased DMN-TPN FC [functional coupling], especially in the presence of preserved thalamocortical FC, is not an index of reduced consciousness but rather a change in the specific mode or style of consciousness.

Increased DMN-TPN coupling (or decreased inverse coupling) has been observed in patients with schizophrenia; however, it is not known how this relates to symptomatology. Increased DMN-TPN coupling has been found in people at high risk of psychosis and an inability to distinguish between one’s internal world and the external environment, sometimes referred to as “disturbed ego boundaries,” is a hallmark of early psychoses and the psychedelic state. For example, one of our volunteers reported the following after psilocybin: “It was quite difficult at times to know where I ended and where I melted into everything around me.” And the following account is from a patient experiencing early psychotic symptoms: “My personality is in danger … my ‘self’ is beginning to disappear.”

It is intriguing to consider whether increased DMN-TPN FC can explain such phenomena. Disturbed ego boundaries is a key component of spiritual-type experiences. It is curious therefore that increased DMN-TPN coupling has been found in experienced mediators, especially those practicing a form of meditation known as “nondual awareness,” which specifically promotes a unitary state of awareness in which there is no distinction between the subject and object. Supplementing the mapping between DMN activity and the sense-of-self, decreased DMN activity has also been found in meditation and the psychedelic state. There is increasing evidence that DMN functioning is related to the sense-of-self or “the ego,” and “ego dissolution” is commonly described in meditation and the psychedelic state. For example, one of our volunteers reported after psilocybin: “That was real ego death stuff, a total dissolving of the ego-boundaries … I only existed as a concept … as an idea.”

Returning to the depersonalization book, there’s a very interesting section devoted to “flashbacks.” Interestingly, these are commonly reported as feeling “exactly like” the depersonalization feelings caused by the drug. The book makes a strong argument that flashback problems are just a special case of “normal” depersonalization/derealization disorder. Having a bad time on drugs is intense and traumatic, and it makes sense that that would be followed by depersonalization. The experience of panic is often associated with depersonalization, and panic is induced by mCPP, a 5-HT2C agonist. Psychedelics are mixed 5-HT2A/5-HT2C partial agonists, so anxious feelings are an inherent risk. Tryptamine hallucinogens are additionally agonists at the 5-HT1A receptor, like cannabidiol and buspirone. This person’s trip report contains the opinion that tryptamines evoke less anxiety than phenethylamines.

It makes sense that multiple drugs could overlap in producing an abstract “sense of unreality,” since they produce reward in many different ways. Oftentimes people with flashback problems use a hallucinogen, then develop problems after using cannabis later.  Maybe “increased default mode network-task positive network coupling” is the common denominator for the surreal feelings produced by drugs, in the same way that dopamine is the common denominator for their reinforcing effects.

Panic isn’t the only thing that causes depersonalization, though. There’s also “emotional abuse,” which is a whole topic unto itself.