Sunday, May 31, 2015

Capgras for Cats and Canaries

Capgras syndrome is the delusion that a familiar person has been replaced by a nearly identical duplicate. The imposter is usually a loved one or a person otherwise close to the patient.

Originally thought to be a manifestation of schizophrenia and other psychotic illnesses, the syndrome is most often seen in individuals with dementia (Josephs, 2007). It can also result from acquired damage to a secondary (dorsal) face recognition system important for connecting the received images with an affective tone (Ellis & Young, 1990).1 Because of this, the delusion crosses the border between psychiatry and neurology.

The porous etiology of Capgras syndrome raises the question of how phenomenologically similar delusional belief systems can be constructed from such different underlying neural malfunctions. This is not a problem for Freudian types, who promote psychodynamic explanations (e.g., psychic conflict, regression, etc.). For example, Koritar and Steiner (1988) maintain that “Capgras' Syndrome represents a nonspecific symptom of regression to an early developmental stage characterized by archaic modes of thought, resulting from a relative activation of primitive brain centres.”

The psychodynamic view was nicely dismissed by de Pauw (1994), who states:
While often ill-founded and convoluted, these formulations have, until recently, dominated many theoretical approaches to the phenomenon. Generally post hoc and teleological in nature, they postulate motives that are not introspectable and defence mechanisms that cannot be observed, measured or refuted. While psychosocial factors can and often do play a part in the development, content and course of the Capgras delusion in individual patients it remains to be proven that such factors are necessary and sufficient to account for delusional misidentification in general and the Capgras delusion in particular.

Canary Capgras

Although psychodynamic explanations were sometimes applied 2 to cases of Capgras syndrome for animals,3 other clinicians report that the delusional misindentification of pets can be ameliorated by pharmacological treatment of the underlying psychotic disorder. Rösler et al. (2001) presented the case of “a socially isolated woman who felt her canary was replaced by a duplicate”:
Mrs. G., a 67-year-old woman, was admitted for the first time to a psychiatric hospital for late paraphrenia. ... She had been a widow for 11 years, had no children, and lived on her own with very few social contacts. Furthermore, she suffered from concerns that her canary was alone at home. She was delighted with the suggestion that the bird be transferred to the ward. However, during the first two days she repeatedly asserted that the canary in the cage was not her canary and reported that the bird looked exactly like her canary, but was in fact a duplicate. There were otherwise no misidentifications of persons or objects.

Earlier, Somerfield (1999) had reported a case of parrot Capgras, also in an elderly woman with a late-onset delusional disorder:
I would like to report an unusual case of a 91-year-old woman with a 10-year history of late paraphrenia (LP) and episodes of Capgras syndrome involving her parrot. She was a widow of 22 years, nulliparous, with profound deafness and a fiercely independent character.  The psychotic symptoms were usually well controlled by haloperidol 0.5 mg orally. However, she was periodically non-compliant with medication, resulting in deterioration of her mental state, refusal of food and her barricading herself in her room to stop her parrot being stolen. At times she accused others of “swapping” the parrot and said the bird was an identical imposter. There was no misidentifcation of people or objects. Her symptoms would attenuate rapidly with reinstatement of haloperidol.

Both of these patients believed their beloved pet birds had been replaced by impostors, but neither of them misidentified any human beings. Clearly, this form of Capgras syndrome is different from what can happen after acquired damage to the affective face identification system (Ellis & Young, 1990). Is there an isolated case of sudden onset Capgras for animals that does not encompass person identification as well? I couldn't find one.

A Common Explanation?

Despite these differences, Ellis and Lewis (2001) suggested that “It seems parsimonious to seek a common explanation for the delusion, regardless of its aetiology.” I'm not so sure. If that's true, then haloperidol should effectively treat all instances of Capgras syndrome, including those that arise after a stroke. And there's evidence suggesting that antipsychotics would be ineffective in such patients.

Are there systematic differences in the symptoms shown by Capgras patients with varying etiologies? Josephs (2007) reviewed 47 patient records and found no major differences between the delusions in patients with neurodegenerative vs. non-neurodegenerative disorders. In all 47 cases, the delusion involved a spouse, child, or other relative. {There were no cases involving animals or objects.}

The factors that did differ were age of onset (older in dementia patients) and other reported symptoms (e.g., visual hallucinations 4 in all patients with Lewy body dementia, LBD). In this series, 81% of patients had a neurodegenerative disease, and only 4% had schizophrenia [perhaps the Capgras delusion was under-reported in the context of wide-ranging delusions?]. Other cases were due to methamphetamine abuse (4%) or sudden onset brain injury, e.g. hemorrhage (11%).

Interestingly, Josephs puts forth dopamine dysfunction as a unifying theme, in line with Ellis and Lewis's general suggestion of a common explanation. The pathology in dementia with Lewy bodies includes degeneration of neurons containing dopamine and acetylcholine. The cognitive/behavioral symptoms of LBD overlap with those seen in Parkinson's dementia, which also involves degeneration of dopaminergic neurons. But dopamine-blocking antipsychotics like haloperidol should not be used in treating LBD. So from a circuit perspective, using “dopamine dysregulation” as a parsimonious explanation isn't really an explanation. And this conception doesn't fit with the neuropsychological model (shown at the bottom of the page).

I'm not a fan of parsimony in matters of brain function and dysfunction. We don't know why one person thinks her canary has been replaced by an impostor, another thinks her husband has been replaced by a woman, while a third is convinced there are six copies of his wife floating around.5 I don't expect there to be a unifying explanation. The BRAIN Initiative and the Human Brain Project will teach us absolutely nothing about the content of delusions. Ultimately, the study of Capgras and other delusional misidentification syndromes present a challenging puzzle for those of us seeking neural explanations of thought and behavior.


1 From Ellis and Young (1990). Also see figure below.
Bauer (1984, 1986) advanced the view that there are two routes to facial recognition. The main route runs from visual cortex to temporal lobes via the inferior longitudinal fasciculus....the 'vental route' corresponds to the system responsible for overt or conscious recognition, and it is the route which typically is damaged in cases of prosopagnosia. The other, described as the 'dorsal route', runs between the visual cortex and the limbic system, via the inferior parietal lobule, and is sometimes intact in prosopagnosic patients. It is this latter route which ... gives the face its emotional significance and hence, when the ventral route is selectively damaged, can give rise to covert recognition (i.e. recognition at an unconscious level).

2 Canine Capgras:
Reports 2 separate cases (a 76-yr-old woman and a 57-yr-old woman) in which the S believed that her pet dog had been replaced by an identical double. The psychodynamic issues that these cases raise are discussed. [NOTE: I don't have access to this article, sorry I can't say more.] In the Capgras delusion the double is usually a key figure in the life of the patient.

3 Capgras for animals was dubbed zoocentric Capgras syndrome by Ehrt (1999). He presented the “case of a 23-year old women who had the delusional belief that her cat had been replaced by the cat of her former boy-friend.”

4 There are a number of interesting hypotheses on why visual hallucinations are so common in Lewy body dementias.

5 Unless he's a character in Orphan Black... But really, why six copies instead of three? What I mean here is an explanation beyond the trivial: one person lives alone with a canary, while the other two live with a spouse.


de Pauw KW. (1994). Psychodynamic approaches to the Capgras delusion: a critical historical review. Psychopathology 27(3-5):154-60.

Ellis HD, Lewis MB. (2001). Capgras delusion: a window on face recognition. Trends Cogn Sci. 5(4):149-156.

Ellis, H., & Young, A. (1990). Accounting for delusional misidentifications. The British Journal of Psychiatry, 157 (2), 239-248 DOI: 10.1192/bjp.157.2.239

Josephs, K. (2007). Capgras Syndrome and Its Relationship to Neurodegenerative Disease. Archives of Neurology, 64 (12) DOI: 10.1001/archneur.64.12.1762

Koritar E, Steiner W. (1988). Capgras' syndrome: a synthesis of various viewpoints. Can J Psychiatry 33(1):62-6.

Rösler, A., Holder, G., & Seifritz, E. (2001). Canary Capgras. The Journal of Neuropsychiatry and Clinical Neurosciences, 13 (3), 429-429 DOI: 10.1176/jnp.13.3.429

Somerfield D. (1999). Capgras syndrome and animals. Int J Geriatr Psychiatry 14(10):893-4.

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Saturday, May 16, 2015

Shooting the Phantom Head (perceptual delusional bicephaly)

I have two heads
Where's the man, he's late

--Throwing Muses, Devil's Roof

Medical journals are enlivened by case reports of bizarre and unusual syndromes. Although somatic delusions are relatively common in schizophrenia, reports of hallucinations and delusions of bicephaly are rare. For a patient to attempt to remove a perceived second head by shooting and to survive the experience for more than two years may well be unique, and merits presentation.

--David Ames, British Journal of Psychiatry (1984)

In 1984, Dr. David Ames of Royal Melbourne Hospital published a truly bizarre case report about a 39 year old man hospitalized with a self-inflicted gunshot wound through the left frontal lobe (Ames, 1984). The man was driven to this desperate act by the delusion of having a second head on his shoulder. The interloping head belonged to his wife's gynecologist.

In an even more macabre twist, his wife had died in a car accident two years earlier..... and the poor man had been driving at the time!

Surprisingly, the man survived a bullet through his skull (in true Phineas Gage fashion). After waking from surgery to remove the bullet fragments, the patient was interviewed:
He described a second head on his shoulder. He believed that the head belonged to his wife's gynaecologist, and described previously having felt that his wife was having an affair with this gynaecologist, prior to her death. He described being able to see the second head when he went to bed at night, and stated that it had been trying to dominate his normal head. He also stated that he was hearing voices, including the voice of his wife's gynaecologist from the second head, as well as the voices of Jesus and Abraham around him, conversing with each other. All the voices were confirming that he had two heads...

I'm two headed one free one sticky
--Throwing Muses, Devil's Roof

The other head kept trying to dominate my normal head, and I would not let it. It kept trying to say to me I would lose, and I said bull-shit ... and decided to shoot my other head off.”

A gun was not his first choice, however... he originally wanted to use an ax.

He stated that he fired six shots, the first at the second head, which he then decided was hanging by a thread, and then another one through the roof of his mouth. He then fired four more shots, one of which appeared to have gone through the roof of his mouth and three of which missed. He said that he felt good at that stage, and that the other head was not felt any more. Then he passed out. Prior to shooting himself, he had considered using an axe to remove the phantom head.

Not surprisingly, the patient was diagnosed with schizophrenia and given antipsychotics.
He was seen regularly in psychiatric out-patients following this operation and by March, stated that the second head was dead, that he was taking his chlorpromazine regularly, and that he had no worries.  [This was Australia, after all.]

Unfortunately, the man died two years later from a Streptococcus pneumoniae infection in his brain.  Ames (1984) concluded his lively and bizarre case report by naming the singular syndromeperceptual delusional bicephaly”:
This case illustrates an interesting phenomenon of perceptual delusional bicephaly; the delusion caused the patient to attempt to remove the second head by shooting. It is notable that following his head injury and treatment with chlorpromazine, the initial symptoms resolved, although he was left with the problems of social disinhibition and poor volition, typical of patients with frontal lobe injuries.

As far as I know, this specific delusion has not yet been depicted in a horror film (or in an episode of Perception or Black Box).


Ames, D. (1984). Self shooting of a phantom head The British Journal of Psychiatry, 145 (2), 193-194 DOI: 10.1192/bjp.145.2.193

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Tuesday, May 05, 2015

Tylenol Doesn't Really Blunt Your Emotions

A new study has found that the pain reliever TYLENOL® (acetaminophen) not only dampens negative emotions, it blunts positive emotions too. Or does it?

Durso and colleagues (2015) reckoned that if acetaminophen can lessen the sting of psychological pain (Dewall et al., 2010; Randles et al., 2013) — which is doubtful in my view then it might also lessen reactivity to positive stimuli. Evidence in favor of their hypothesis would support differential susceptibility, the notion that the same factors govern reactivity to positive and negative experiences.1 This outcome would also contradict the framework of acetaminophen as an all-purpose treatment for physical and psychological pain.

The Neurocritic is not keen on TYLENOL® as a remedy for existential dread or social rejection. In high doses acetaminophen isn't great for your liver, either. And a recent meta-analysis even showed that it's ineffective in treating lower back pain (Machado et al., 2015)...

But I'll try to be less negative than usual. The evidence presented in the main manuscript supported the authors' hypothesis. Participants who took acetaminophen rated positive and negative IAPS pictures as less emotionally arousing compared to a separate group of participants on placebo. The drug group also rated the unpleasant pictures less negatively and the pleasant pictures less positively. “In all, rather than being labeled as merely a pain reliever, acetaminophen might be better described as an all-purpose emotion reliever,” they concluded (Durso et al., 2015).

Appearing in the prestigious Journal of Psychological Acetaminophen Studies, the paper described two experiments on healthy undergraduates, both of which yielded a raft of null results.

Wait a minute..... what? How can that be?

The main manuscript reported the results collapsed across the two studies, and the Supplemental Material presented the results from each experiment separately. Why does this matter?
Eighty-two participants in Study 1 and 85 participants in Study 2 were recruited to participate in an experiment on “Tylenol and social cognition” in exchange for course credit. Our stopping rule of at least 80 participants per study was based on previously published research on acetaminophen (DeWall et al., 2010; Randles et al., 2013), in which 30 to 50 participants were recruited per condition (i.e., acetaminophen vs. a placebo).  ... The analyses reported here for the combined studies are reported for each study separately in the Supplemental Material available online.

What this means is that the authors violated their stopping rule, and recruited twice the number of participants as originally planned. Like the other JPAS articles, this was a between-subjects design (unfortunately), and there were over 80 participants in each condition (instead of 30 to 50).

After running Experiment 1, the authors were faced with results like these:
As expected, however, a main effect of treatment (though not significantly significant in this study) was obtained, F(1,72) = 2.15, p = .147, ηp2 = .029, as was the predicted interaction (although it was not statistically significant in this study), F(3.3, 240.3) = 1.15, p = .330, ηp2 = .016. Contrast analyses indicated that participants taking acetaminophen were marginally significantly less emotionally aroused by extremely pleasant stimuli (M = 5.01, SD = 1.75) than were participants taking placebo (M = 5.65, SD = 1.55), t(72) = 1.67, p = .099. Similarly, participants receiving acetaminophen were less emotionally aroused by extremely unpleasant stimuli (M = 6.88, SD = 1.25) than were participants assigned the placebo condition (M = 7.23, SD = 1.84), although this difference was not statistically significant in this study, t(72) = 0.96, p = .341. Furthermore, participants taking acetaminophen tended to be less emotionally aroused by moderately pleasant stimuli (M = 2.91, SD = 1.64) than participants taking placebo (M = 3.49, SD = 1.89), t(72) = 1.44, p = .155, and participants taking acetaminophen also tended to be less emotionally aroused by moderated unpleasant stimuli (M = 4.68, SD = 1.42) than participants taking placebo (M = 5.25, SD = 2.02), t(72) = 1.42, p = .161, although these differences were not statistically significant in this study. 

Wow, what a disappointment to get these results. Nothing looks statistically significant!

Let's look at Experiment 2:
...Contrast analyses revealed that participants taking acetaminophen tended to rate extremely unpleasant stimuli (M = -3.39, SD = 1.14) less negatively than participants receiving placebo (M = -3.74, SD = 0.74), t(77) = 1.60, p = .115, though this contrast was not itself statistically significant within this study. Participants taking acetaminophen also rated extremely pleasant stimuli (M = +2.51, SD = 1.07) significantly less positively than participants receiving placebo (M = +3.19, SD = 0.88), t(77) = 3.06, p = .003.

Participants taking acetaminophen also tended to evaluate moderately pleasant stimuli (M = +1.15, SD = 0.91) less positively than participants receiving placebo (M = +1.42, SD = 0.89), t(77) = 1.30, p = .198, although this difference was not statistically significant in this study. Finally, participants taking acetaminophen tended to rate moderately unpleasant stimuli less negatively (M = -1.84, SD = 0.99) than participants taking placebo (M = -1.93, SD = 0.95), although this difference was not significant in this study, t(77) = 0.42, p = .678. [NOTE: "tended"? really?] Evaluations of neutral stimuli surprisingly differed as a function of treatment, t(77) = 2.94, p = .004, such that participants taking acetaminophen evaluated these stimuli significantly less positively (M = -0.05, SD = 0.42) than did participants taking placebo (M = +0.22, SD = 0.38).

One of the arguments that acetaminophen affects ratings of emotional stimuli specifically (both positive and negative) is that it does not affect ratings for neutral stimuli. Yet it did here. So in the paragraphs above, extremely pleasant stimuli and neutral stimuli were both rated as less positive by the drug group, but ratings for extremely unpleasant, moderately pleasant, and moderately unpleasant pictures did not differ between drug and placebo groups.

The subjective emotional arousal ratings fared better than the picture ratings in Experiment 2, but there were still some unexpected and non-significant results. Overall, support for the “acetaminophen as an all-purpose emotion reliever” was underwhelming when the studies are examined singly (which is how they were run). 2

[Right about now you're saying, “Hey! I thought you said you'd be less negative here!”]

Let's accept that the combined results reported in the main manuscript present a challenge to the “acetaminophen as a psychological pain reliever” view, and support the differential susceptibility hypothesis. To convince those of us outside the field of social psychology, it would be beneficial to: (1) design within-subjects experiments, and (2) seriously consider possible mechanisms of action, beyond speculations about serotonin and (gasp!) 5-HTTLPR. For instance, why choose acetaminophen (which may act via the spinal cord) and not aspirin or ibuprofen? 3

At the risk of sounding overbearing and pedantic, I hereby issue the following friendly suggestions to all TYLENOL® psychology researchers...

The Proper Pharmacological Study Design Challenge

(1) Please consider using a double-blind, randomized crossover design, like studies that have examined IAPS picture ratings after acute administration of SSRI antidepressants or placebo in healthy participants (Kemp et al., 2004; van der Veen et al., 2012; Outhred et al., 2014).

Speaking of SSRIs, did you know that citalopram did not alter IAPS valence or arousal ratings relative to placebo (Kemp et al., 2004)? Or that paroxetine produced only minor effects on valence and arousal ratings for two of the eight conditions (van der Veen et al., 2012)? 4 What are the implications of these findings for your theoretical framework, that an OTC pain reliever supposedly has a greater impact on emotional processing than a prescription antidepressant? And that before the recent JPAS papers, no one has ever suspected that TYLENOL® affects reactions to emotionally evocative stimuli or David Lynch films?

(2) Please consider that acetaminophen may act via COX-1, COX-2, COX-3, peroxidase, nitric oxide synthase, cannabinoid receptors, and/or descending serotoninergic projections to the spinal cord (Toussaint et al., 2010) before mentioning the anterior cingulate cortex or the serotonin transporter gene. Just another friendly suggestion.

I usually give all my ideas away for free, but if you're interested in hiring me as a consultant, please leave a comment.

ADDENDUM (May 6 2015): A comment by Dr. R (who developed the Replication-Index) said there was nothing wrong with combining the two studies. Study 1 was non-significant but Study 2 was significant, and combined the results were statistically credible (although I'm not exactly sure which of the many tests he checked). Perhaps one source of trouble was that Durso et al.'s estimated number of participants was based on inflated effect sizes in the earlier papers...


1 Turns out differential susceptibility is more or less The Orchid and the Dandelion, or as author David Dobbs puts it, “some of the genes and traits generating our greatest maladies and misdeeds — depression, anxiety, hyper-aggression, a failure to focus — also underlie many of our greatest satisfactions and success." I don't really see how this acetaminophen study informs the differential susceptibility hypothesis, which is based on individual differences (beyond a metaphorical kinship, perhaps).

2 But then I missed the memo from Psych Sci on “recently recommended approaches to presenting the results of multiple studies through combined analyses.”  [paging @mc_hankins...]

3 I know the original social rejection study used Tylenol, but why does everyone persist in doing so?? I was pleased to see that in the press release, first author Geoffrey Durso said they're branching out to test ibuprofen and aspirin.  [There, something positive.]

4 To be precise, participants gave lower arousal ratings to high arousal, low valence pictures and slightly lower valence ratings to high arousal, high valence pictures. The other six cells in the arousal/pleasure ratings of high/low arousal, high/low pleasure were no different on drug vs. placebo.


Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 21:931-7.

Durso, G., Luttrell, A., & Way, B. (2015). Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli. Psychological Science DOI: 10.1177/0956797615570366

Kemp AH, Gray MA, Silberstein RB, Armstrong SM, Nathan PJ. (2004). Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans. Neuroimage 22:1084-96.

Machado GC, Maher CG, Ferreira PH, Pinheiro MB, Lin CW, Day RO, McLachlan AJ, Ferreira ML. (2015). Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 350:h1225.

Outhred T, Das P, Felmingham KL, Bryant RA, Nathan PJ, Malhi GS, Kemp AH. (2014). Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women. J Psychiatry Neurosci. 39:267-75.

Randles D, Heine SJ, Santos N. (2015). The common pain of surrealism and death: acetaminophen reduces compensatory affirmation following meaning threats. Psychol Sci. 24:966-73.

van der Veen FM, Jorritsma J, Krijger C, Vingerhoets AJ. (2012). Paroxetine reduces crying in young women watching emotional movies. Psychopharmacology 220:303-8.

Better get this woman a damn fine cup of coffee and 1000 mg of TYLENOL®

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