The Mental Health of Lonely Marijuana Users

Mr. Lonely ¹

Does Smoking Pot Offer Relief to the Lonely?  A new paper by the original Tylenol and social pain researchers claims that it does (Deckman et al., 2013). Let's take a closer look.

Comfortably Numb: Marijuana Use Reduces Social Pain, Research Finds

Marijuana use buffers people from experiencing social pain, according to research published online on May 14 in Social Psychological and Personality Science.

"Prior work has shown that the analgesic acetaminophen, which acts indirectly through CB1 receptors, reduces the pain of social exclusion," Timothy Deckman of the University of Kentucky and his colleagues wrote in the study. "The current research provides the first evidence that marijuana also dampens the negative emotional consequences of social exclusion on negative emotional outcomes."

You could be forgiven if you thought, as I initially did, that the University of Kentucky IRB must hold a liberal view on the administration of controlled substances to undergrads participating in psychology experiments. But that's not what happened here... the data are entirely correlational, based on self-report, and largely problematic (in my view).


Marijuana Lowers Self-Worth and Worsens Mental Health in Those Who Are Not Lonely

That's my interpretation of the article, which is SO clunky compared to the fun and breezy query, Can Marijuana Reduce Social Pain? ²

The paper begins with the premise that "Social and physical pain share common overlap at linguistic, behavioral, and neural levels" (Deckman et al., 2013). So let's give a pain reliever to reduce the sting of rejection!  A critique of the original work asked why the authors chose Tylenol, as opposed to an NSAID like aspirin, ibuprofen, or naproxen. In the current study they tried to develop a mechanistic account of why acetaminophen might reduce social pain:

Prior research has shown that acetaminophen—an analgesic medication that acts indirectly through cannabinoid 1 receptors—reduces the social pain associated with exclusion. Yet, no work has examined if other drugs that act on similar receptors, such as marijuana, also reduce social pain.

The problem is that acetaminophen's mechanism of action is surprisingly unclear (Toussaint et al., 2010). One prominent hypothesis claims that Tylenol might exert its analgesic effects through descending serotonergic pathways at the level of the spinal cord. In fact, the paper that Deckman et al. cited in favor of cannabinoid 1 (CB₁) receptors describes a very complex pathway that includes indirect involvement of CB₁, with actual pain suppression occurring in the spinal cord. ³

An even more basic question: if acetaminophen acts through CB₁ receptors, then why isn't it a potential drug of abuse, or known by experienced pharmanauts for its psychoactive properties?  The drug experience vault Erowid says:

Acetaminophen is a non-salicylate analgesic and antipyretic (pain killer and fever reducer). It is a common over-the-counter pain medication found in hundreds of products around the world. At higher doses it is known to cause liver-damage and has a low therapeutic index (ratio of effective dose to toxic dose), making it dangerous when included in recreationally used pharmaceuticals [e.g., Tylenol with codeine]. It is not known to be psychoactive.

On the other hand, we all know that cannabis is psychoactive. The design of the cannabis study included cross-sectional national survey data, a two year longitudinal survey of 400 high school students, and a Mechanical Turk-implemented version of cyberball, an online game to simulate social exclusion. In all cases, participants reported their marijuana use, and this was related to the variables of interest.

I'll focus on the national survey data in this post, which comprised Study 1 (Marijuana Use Buffers Lonely People From Lower Self-Worth and Self-Rated Mental Health) and Study 2 (Marijuana Use Predicts Fewer Major Depressive Episodes Among the Lonely).

Study 1 used data from the National Comorbidity Survey: Baseline (NCS-1), 1990-1992 (ICPSR 6693), which you can download for yourself. The survey recruited 8,098 individuals from the ages of 15 to 54 living in the U.S., and included over 4,000 variables. Only four variables were chosen for the present study: self-reported loneliness (1= often, 4 = never), marijuana use (0 = none, 1 = daily, 8 = once or twice a year), self-worth (1 = high, 4 = low), and overall mental health (1 = excellent, 5 = poor).

Loneliness was used as a proxy for social pain. Contrary to what the headlines suggested, the impact of pot smoking on social pain was not directly examined. Instead, the study assessed the effects of loneliness (high, low), marijuana use (high, low) and their interaction on self-worth and mental health.

Loneliness and pot smoking interacted to predict feelings of self-worth [B = 0.03, t(5609) = 2.20, p = .03]. Given the huge number of participants, this level of statistical significance is not very impressive.

Fig. 1 (modified from Deckman et al., 2013). Study 1: Marijuana use moderates the relationship between loneliness and self-reported feelings of self-worth. [NOTE: items were reverse-scored for display purposes.]


For lonely people, the amount of pot smoked didn't make too much of a difference in their self-worth (see red arrow above).  For socially connected people, greater marijuana use resulted in lower self-worth, although it's not clear this was significant (pairwise statistical tests were not reported).

I also question how the High Marijuana Use and Low Marijuana Use groups were determined, because over 5,000 participants did not smoke pot at all in the last 12 months. Does the heavy use group combine those who smoke 6 joints a year with those who smoke daily?

Table depicting the mean level of loneliness (1=often to 4=never) for participants at 9 levels of pot smoking (0=none, 1=daily, 8=once or twice a year). Unlike the figure above, the values were not reverse-scored. Data from the National Comorbidity Survey: Baseline (NCS-1), 1990-1992 (ICPSR 6693).


In the lonely group, the frequency of marijuana use had even less of an impact on self-rated mental health. In contrast, heavy pot use resulted in worse mental health among the socially connected. A modest loneliness by marijuana use interaction was observed for mental health [B = 0.03, t(5609) = 2.07, p = .04], similar to what was seen for self-worth.

Fig. 2 (modified from Deckman et al., 2013). Study 1: Marijuana use moderates the relationship between loneliness and self-reported mental health. [NOTE: items were reverse-scored for display purposes.]


Looking at Fig. 2 above, it's clear that marijuana use does not buffer the lonely from the negative consequences of social pain: the black circle and gray square are overlapping. But the authors interpret this result differently:

Marijuana use buffered the lonely from both negative self-worth and poor mental health. This evidence suggests that at relatively high levels of social pain, marijuana use lessens negative consequences of social pain.

As part of the six sentence Discussion of Study 1, they point out one weakness to motivate Study 2:

This study contained some limitations. First, it only assessed self-ratings of both self-worth and mental health. If marijuana use weakens the relationship between social pain and self-reported psychological well-being, then there should also be a lower rate of validated clinical diagnoses of poor psychological well-being.
. . .
To address the limitation of Study 1, Study 2 sought to show that marijuana buffered lonely participants from experiencing a standardized diagnosis of poor psychological well-being. Study 2 used a different nationally representative sample from Study 1 to test this hypothesis.

HOWEVER, the dataset used in Study 1 has extensive information on DSM-III-R diagnoses (including depression) for the majority of participants, so I'm not sure why this wasn't included. Study 2 used data from the National Comorbidity Survey Replication (NCS-R; Kessler & Merikangas, 2004), a different national sample of 10,000 respondents.

Speaking of replication, Deckman et al. should have been able to completely replicate the pot × loneliness analyses for self-worth, self-rated mental health, and DSM depression in both National Comorbidity Samples. I'm not sure why they didn't.

For Study 2, non-users were excluded (unlike in Study 1). The final sample included 537 participants with info on loneliness, marijuana use, and whether they experienced a major depressive episode during the past year. Once again, the results demonstrated that if you're lonely, smoking a lot vs. a little pot will not affect whether you'll experience a major depressive event (red arrow below). If you're not lonely, heavy marijuana use increases the risk of major depression.

Fig. 3 (modified from Deckman et al., 2013). Study 2: Marijuana use moderates the relationship between loneliness and a having a DSM-IV major depressive event in the past 12 months.


Study 3, a survey of 400 high school students, was the most puzzling of all. At Time 1 the students were asked about loneliness, lifetime marijuana use, and depression. Two years later, they were asked again about depression, using the Behavior Assessment System for Children (second edition), but not about marijuana use and loneliness (which could have changed drastically in 2 years).

At any rate, lonely heavy pot users were the least depressed of all at Time 2. I'm not sure how to interpret this; the pattern differs from what was seen in adults. Maybe the lonely heavy pot users at Time 1 bonded with their peer group over two years and were no longer lonely at Time 2.

Fig. 4 (modified from Deckman et al., 2013). Study 3: Marijuana use moderates the relationship between loneliness and depression over 2 years in adolescents. 


Conflicting earlier studies in adolescents have suggested that lonely high school students are more likely (Page, 2000) and less likely (Grunbaum et al., 2000) to use marijuana. A recent study indicated that heavy marijuana users are more likely to engage in self-injury (Giletta et al., 2012), but this was true only for Americans and not for Dutch and Italian students. I imagine there's a huge literature on these issues, but it wasn't addressed at all in the present paper.

Overall, I don't think the authors have demonstrated that marijuana reduces social pain, at least not in adults. They used a very select set of questions from huge, comprehensive national surveys and then called this a limitation of the study:

Another potential limitation to some of the above studies lies in how social pain was measured. In Studies 1–3, single-item measures of loneliness were used as a proxy for social pain. These studies use large community sample data sets and thus our ability to include numerous measures was limited.

There were many other questions that could have assessed social pain in NCS-1 and NCS-R, including a series of questions about friendships, e.g. "How much do your friends really care about you--a lot, some, a little, or not at all?"

Has this paper advanced the agenda of the social pain/physical pain isomorphists? We already knew that opiates were good at alleviating both types of pain. And it's a truism to say that people turn to alcohol and all sorts of recreational drugs to dull the pain of a lonely existence. For the most part, we assume this isn't a healthy way to cope. Some studies suggests that depression is decreased in heavy marijuana users (Denson & Earleywine, 2006) but others find an increase (Pacek et al., 2013).

In sum, Deckman et al., (2013) presented evidence that heavy marijuana use is detrimental to the mental health of socially connected individuals and not especially effective in buffering lonely users from social pain.


Footnotes

¹ However, please note that highly reliable source TMZ claims "Akon doesn't drink ... Akon doesn't smoke ... but Akon was pretty damn surprised when he found out his pal Justin Bieber might be doin' both."

² University press offices!! I'm sure you'd love to hire me to write your press releases. Price quotes are available upon request, please leave a comment.

³ You might also want to know something about the distribution of CB₁ receptors in the anterior cingulate cortex, the purported locale of physical/social pain overlap.

⁴ Survey questions were:

LONELY - During the past 30 days how often did you feel lonely?
POT - On the average, how often in the past 12 months have you used marijuana or hashish? Just
WORTHY - I feel I am a person of worth, at least equal with others.
MENTAL HEALTH - How would you rate your overall mental health? Is it excellent, very good, good, fair, or poor?

Data for these four questions were available from 5,631 participants. Ratings were standardized, reverse-scored, and analyzed using weighted least squares regression.


References

Deckman, T., DeWall, C., Way, B., Gilman, R., & Richman, S. (2013). Can Marijuana Reduce Social Pain? Social Psychological and Personality Science. DOI: 10.1177/1948550613488949

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.

Toussaint K, Yang X, Zielinski M, Reigle K, Sacavage S, Nagar S, Raffa R. (2010). What do we (not) know about how paracetamol (acetaminophen) works? Journal of Clinical Pharmacy and Therapeutics 35 (6), 617-638.

What RDoC Research Might Look Like

The month of May is a violent thing
In the city their hearts start to sing
Well, some people sing, it sounds like they're screaming
I used to doubt it, but now I believe it

Month Of May
   ------The Arcade Fire

Today is Mental Health Month Blog Day, sponsored by the American Psychological Association (APA). It's designed to:

...educate the public about mental health, decrease stigma about mental illness, and discuss strategies for making lasting lifestyle and behavior changes that promote overall health and wellness.

If the public has been following the recent hullabaloo about how to diagnose mental illnesses, they might be confused about the current and future direction of the field. How did we get here?

As most of you know, the American Psychiatric Association (the other APA) is about to release its updated Diagnostic and Statistical Manual of Mental Disorders, the much maligned DSM-5. Weeks before the big launch, however, the National Institute of Mental Health (NIMH) stole the show by announcing that it will be re-orienting its research away from DSM categories:

...While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure.

Instead, the Research Domain Criteria (RDoC) framework would become the preferred method for organizing biologically-based research on mental illnesses, with the ultimate goal of constructing a new classification scheme.

This caused quite a commotion, leading many to comment on NIMH's shocking repudiation of DSM-5. However, to long-time observers of RDoC's development, this was not a surprise. And the initial lack of clarity on the distinction between the RDoC Dimensional Approach for Research vs. DSM-5 for Diagnosis didn't help matters, nor did the uncertainty about whether NIMH would fund DSM-based research at all.¹

NIMH issued a press release on May 13 to clarify its position:

DSM-5 and RDoC: Shared Interests

Thomas R. Insel, M.D., director, NIMH
Jeffrey A. Lieberman, M.D., president-elect, APA

NIMH and APA have a shared interest in ensuring that patients and health providers have the best available tools and information today to identify and treat mental health issues, while we continue to invest in improving and advancing mental disorder diagnostics for the future.

Today, the APA's Diagnostic and Statistical Manual of Mental Disorders (DSM), along with the International Classification of Diseases (ICD) represents the best information currently available for clinical diagnosis of mental disorders  Patients, families, and insurers can be confident that effective treatments are available and that the DSM is the key resource for delivering the best available care. The NIMH has not changed its position on DSM-5. As NIMH’s Research Domain Criteria (RDoC) project website states, “The diagnostic categories represented in the DSM-IV and the International Classification of Diseases-10 (ICD-10, containing virtually identical disorder codes) remain the contemporary consensus standard for how mental disorders are diagnosed and treated.”

Yet, what may be realistically feasible today for practitioners is no longer sufficient for researchers. Looking forward, laying the groundwork for a future diagnostic system that more directly reflects modern brain science will require openness to rethinking traditional categories. It is increasingly evident that mental illness will be best understood as disorders of brain structure and function that implicate specific domains of cognition, emotion, and behavior. This is the focus of the NIMH’s Research Domain Criteria (RDoC) project. RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness.

So what is RDoC, and how might it be applied to new research projects? From the DSM perspective of categorical disorders (e.g, schizophrenia, major depression, and obsessive compulsive disorder), RDoC embraces diagnostic messiness. Patients previously excluded from a study due to comorbidities, or because they don't meet full criteria? Misfits from the "Not Otherwise Specified" (NOS) category? Now they're in. Specifically, the instructions for RFA-MH-14-050 state:

Priority will be given to applications that have a well-justified plan to include patients from multiple diagnostic groups (including Not Otherwise Specified and forme fruste diagnoses) as appropriate for explicating the dimensions and constructs of interest in the study design. Studies that include patients from a single diagnostic group may also be considered if there is a particularly strong justification for examining constructs of interest within one diagnostic category.  A defensible approach might be to study all patients presenting themselves at a specialty clinic, e.g., mood disorders clinic, anxiety clinic, or psychotic disorders clinic, regardless of whether they meet criteria for a particular DSM diagnosis.

One potential pitfall of this approach is the money required to enroll huge numbers of patients. If commonalities in cognitive function or brain circuitry or especially genetic risk factors are to emerge from studying all patients with mood disorder-like symptoms, then sample sizes must be very large to overcome potential noise in the system(s).

The applicant would propose to study one or more of the five different domains, or constructs, that have been fleshed out at NIMH Workshops:

Negative Valence Systems
Positive Valence Systems
Cognitive Systems
Systems for Social Processes
Arousal/Regulatory Systems

The possible units of analysis run the gamut from genes to circuits to behavior, and the studies should use specific tasks (paradigms) and self-report measures, as shown in the Negative Valence Systems matrix below.

Draft Research Domain Criteria Matrix

Animal models of active threat ("fear") like the startle response are pretty well established and would allow a much more detailed analysis of mechanisms, from genes to behavior. In the realm of human research, one example of a proposed project for RFA-MH-14-050 is:

• Evaluation of the relationship between measures of exaggerated fear response, reports of overall distress and anxiety, and chronicity of internalizing disorders

This project could study common and unique aspects of the startle response in patients with phobias, panic disorder, OCD, generalized anxiety, and major depression ("internalizing disorders"), as described in this review article (Vaidyanathan et al.  2011).

Another recent review tackles the neurobiology of reward, which falls under the rubric of Positive Valence Systems. It's a 43 page tour de force with 756 references (Dichter et al., 2012):

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

The idea is to find common neurobiological substrates of altered reward circuitry that cut across DSM-esque categories (e.g., drug and alcohol use disorders, serious gambling problems, mania), where individuals seek out reward without regard to the consequences. At the other end of the spectrum is anhedonia, or the inability to feel pleasure from previously rewarding activities. Anhedonia is often (but not always) seen in major depression and schizophrenia, two disorders usually considered to have little overlap.

Will RDoC succeed in carving out a new nosology and generating a new guidebook? Will it lead to diagnostic tests that can identify specific cognitive, emotional, motivational, or social weaknesses that can be treated with targeted pharmaceuticals, deep brain stimulation, and/or improved psychotherapies?

This quote from Chapter 1 of a 2002 white paper collection indicates the DSM-5 revision committee (a joint APA / NIMH production) didn't exactly expect that all of its goals would be reached (PDF):

"Given the relatively short time frame for generating breakthrough research findings between now [1999] and the probable publication of DSM-V in 2010 [2013], it is anticipated that some of the research agendas suggested in these chapters might not bear fruit until the DSM-VI or even DSM-VII revision processes!"

So don't hold your breath, unless you want to experience severe anoxia.


Footnotes

¹ See the Appendix for a compendium of quotes.


References

Dichter, G., Damiano, C., & Allen, J. (2012). Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings Journal of Neurodevelopmental Disorders, 4 (1) DOI: 10.1186/1866-1955-4-19

Vaidyanathan, U., Nelson, L., & Patrick, C. (2011). Clarifying domains of internalizing psychopathology using neurophysiology Psychological Medicine, 42 (03), 447-459 DOI: 10.1017/S0033291711001528


Appendix

May 6
Matthew Herper (Forbes reporter covering science and medicine): “I spoke to NIMH. This is a broadening, not an exclusion.” ...

DSM-5 Task Force member Dr.  David J. Kupfer strikes back in the NYT, blaming NIMH and the sluggish rate of scientific progress: “The problem that we’ve had in dealing with the data that we’ve had over the five to 10 years since we began the revision process of D.S.M.-5 is a failure of our neuroscience and biology to give us the level of diagnostic criteria, a level of sensitivity and specificity that we would be able to introduce into the diagnostic manual.”


May 7
“Some people have the idea that we’re trying to ditch or diss the DSM and that’s not a fair assessment,” says Insel.

Dr. Bruce Cuthbert: “The sensationalist headlines out there are entirely misleading, and we will continue to support DSM-based research as we increase our portfolio of RDoC grants. RDoC is intended to inform future versions of the ICD and DSM; we have no intention of coming out with a competing system. The implication of this is that the fruits of RDoC are likely to be taken up into the ICD/DSM piecemeal rather than in one entire set, at such times as the evidence for various aspects becomes strong enough to warrant changes to the nosologies.”

Dr. Thomas Insel: “We cannot ‘ditch’ or ‘reject’ terms like schizophrenia or bipolar. We just need to view them as constructs, perhaps including many different disorders that require different treatments or obscuring disorders than cut across the current categories. A symptom-only system will not be sufficient for identifying brain disorders—whether the initial label is dementia or schizophrenia.”

Dr. Cuthbert: “As with most shifts in science, changes in research priorities require a transition. Because almost all clinical researchers today grew up with the DSM system both clinically and in research, it will take some time to get a “feel” for the relationships between DSM disorders and various kinds of RDoC phenomena (both in terms of the types of symptoms, and in overall severity), learn how to write grant applications with the new criteria, and evolve new review criteria. So, there will be a period of some time while these crosswalks are worked out.”


May 8
Dr. Cuthbert: “Using DSM diagnoses for research has become a de facto standard ever since the DSM-III came out in 1980. What we are trying to do is to study neural systems directly because they cut across lots of the dsm disorders. ... We are moving in a new direction. That doesn’t mean that next month we’ll stop accepting DSM diagnoses. It rather is a shift in emphasis.”

RDoC Dimensional Approach for Research vs. DSM-5 for Diagnosis

Dr. Thomas Insel, director of the National Institute of Mental Health (NIMH) in the U.S., recently announced that NIMH will be re-orienting its research away from DSM categories:

...While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.

Patients with mental disorders deserve better. NIMH has launched the Research Domain Criteria (RDoC) project to transform diagnosis by incorporating genetics, imaging, cognitive science, and other levels of information to lay the foundation for a new classification system. Through a series of workshops over the past 18 months, we have tried to define several major categories for a new nosology...

The dimensional approach to studying mental illness was covered in an excellent new blog post by Dr. Russ Poldrack, who describes ongoing work including the Consortium for Neuropsychiatic Phenomics and the Cognitive Atlas project.

I first wrote about the Research Domain Criteria for Classifying Mental Disorders in 2010:

There is no absolute timeline of when these [research] advances might occur. Instead of providing an immediate replacement for DSM and its clinical diagnoses, RDoC is a long-term project to help the research community by defining more biologically based organizational principles for various psychopathologies...

NIMH has been preparing the RDoC criteria for the past 2-3 years, as you can see in the RDoC Publications and in these Proceedings of RDoC Workshops (scroll down). Requests for applications (RFAs) on Dimensional Approaches to Research Classification in Psychiatric Disorders date back to 2011. The workshops and publications haven't been a secret, they've been available all along.¹

Nonetheless, Insel's announcement was treated as a "bombshell", a "potentially seismic move", and a "humiliating blow to the APA." But as 1 Boring Old Man notes, this is old news.

One of the more alarmist posts on the topic was by John Horgan:

Psychiatry in Crisis! Mental Health Director Rejects Psychiatric “Bible” and Replaces With… Nothing

. . .

Now, in a move sure to rock psychiatry, psychology and other fields that address mental illness, the director of the National Institutes of Mental Health has announced that the federal agency–which provides grants for research on mental illness–will be “re-orienting its research away from DSM categories.” Thomas Insel’s statement comes just weeks before the scheduled publication of the DSM-V, the fifth edition of the Diagnostic and Statistical Manual.

Note the foreshadowing here: I do think Dr. Insel's timing in announcing the dimensional RDoC was a deliberate attempt to blunt the media circus that will surround the big DSM-5 release at the APA meeting in 2 weeks.

However, Horgan thinks the timing was more related to President's Obama's ambitious new BRAIN Initiative when he says:

NIMH director Insel doesn’t mention it, but I bet his DSM decision is related to the big new Brain Initiative, to which Obama has pledged $100 million next year. Insel, I suspect, is hoping to form an alliance with neuroscience, which now seems to have more political clout than psychiatry.

This is utterly preposterous, since NIMH has been aligned with "neuroscience" for years (which is apparent when looking at funded projects).² And by "political clout" I assume he means the Society for Neuroscience has more political clout than the American Psychiatric Association (APA). However, it's not likely that NIMH has abandoned APA.

1 Boring Old Man goes much further and points out that A Research Agenda for DSM-V (2002) was a collaboration between APA and NIMH:

Do they really think that we won’t notice that the APA and NIMH are working in tandem – that their efforts are coordinated? Do they think we won’t notice that the "cross cutting" dimensional scheme for the DSM-5 that got dropped is the same idea as the RDoC? The articles that have been popping up all day are playing this as Insel’s NIMH throwing the DSM-5 under the bus. No need. The DSM-5 is already under the bus where it belongs.

bus image © BrokenSphere / Wikimedia Commons

Footnotes

¹ All this activity might not have been apparent to those outside the U.S. funding system, however. Or to the majority of the planet who haven't read old blog posts on the topic.

² On the front page of NIH RePORTER, search 'NIMH' and '1989' (the oldest date available).

Want to remember something? Clenching your fist doesn't help!

Image Credits: fist and brain.

You might have seen this news story the other day:

Want to remember something? Clench your fists!

Giving a speech and need to remember what to say? Just clench your right fist while rehearsing. Then, when it's time to give the speech, clench your left fist, and voila, you’ll recall what you rehearsed! That's what a new study found, which was published April 24 online at PLOS ONE. 

Sounds too easy now, doesn't it? And if you're exclaiming, "that's just too good to be true!" — then you'd be correct.

The new study by Propper et al. (2013) has unleashed a torrent of criticism on Twitter, including this starter by @js_simons.

What motivated such a study in the first place? I'll try to run through the authors' rationale here, starting with statements from the abstract, which are followed by my commentary.

• Unilateral hand clenching increases neuronal activity in the frontal lobe of the contralateral hemisphere.

It's true that unilateral hand movement is executed via motor cortex activity in the opposite hemisphere, so the right hemisphere controls the left hand and vice versa.

• Such hand clenching is also associated with increased experiencing of a given hemisphere’s “mode of processing.”

This statement is based on EEG studies that have looked at alpha power suppression recorded at scalp electrodes over left and right frontal cortex (Harmon-Jones, 2006). The hypothesis is that left hand contractions "activate" (i.e., suppress alpha waves in) the unhappy right hemisphere, thereby producing negative affect, while right hand contractions activate the happy left hemisphere, which results in positive affect. The affective "modes of processing" aspect of this research isn't directly relevant to the Propper et al. (2013) paper, and further discussion is beyond the scope of this post. I'll just say that attributing EEG activity to a specific cortical region is a dicey proposition, because the spatial resolution of the technique isn't great.¹

• Together, these findings suggest that unilateral hand clenching can be used to test hypotheses concerning the specializations of the cerebral hemispheres during memory encoding and retrieval.

Here the EEG research on emotion is being applied to memory.

• We investigated this possibility by testing effects of unilateral hand clenching on episodic memory. The hemispheric Encoding/Retrieval Asymmetry (HERA) model proposes left prefrontal regions are associated with encoding, and right prefrontal regions with retrieval, of episodic memories.

The Hemispheric Encoding/Retrieval Asymmetry (HERA) model of Tulving et al. (1994) postulates that the left prefrontal cortex encodes information into memory, while the right prefrontal cortex retrieves information from memory. This was back in ye olden days of PET using block designs with 40 seconds of one condition subtracted from 40 seconds of another condition. In other words, poor temporal resolution.

The HERA model was revisited and confirmed by its proponents using fMRI data (Habib et al., 2003), but the evidence against it was considerable (Owen, 2003). The general consensus is that HERA has been discredited. In fact, noted memory researcher Dr. Jon Simons posted a comment at the PLOS ONE website explaining why the underlying hypothesis of Propper et al. is problematic (among other issues).

• It was hypothesized that right hand clenching (left hemisphere activation) pre-encoding, and left hand clenching (right hemisphere activation) pre-recall, would result in superior memory. 

Here we're expecting to see better memory in the R/L condition than in the control condition. There is no mention that the other fist-clenching conditions would result in worse performance than in the control condition.

• Results supported the HERA model.

Results did NOT support the HERA model, and I'll explain why below (and you can read the PLOS ONE comment).


In the experiment, participants studied a list of 36 words, engaged in a filler task, and then recalled as many words as possible. Approximately 10 subjects participated in each of 16 conditions, only five of which are reported in the paper. These involved squeezing a small pink ball in one hand (2 sets of 45 sec) before the encoding and the retrieval phases of the study. The control condition did not involve clenching, but the participants held a small pink ball in each hand.²

The five conditions are shown below, named by the hand used during encoding/retrieval. You'll notice that the number of participants in each group (n) is pretty small. I calculated standard deviations from the standard error values to determine effect sizes using this effect size calculator. ³

Although the authors reported the total number of words written down (correct or not) and the number of correct words in Figs. 1 and 2 respectively, the important result is shown in Fig. 3, which takes into account the false alarms, or incorrectly recalled words.

Figure 3 (Propper et al., 2013). Corrected scores as a function of hand clench condition. [NOTE: NENR = None Encoding/None Recall, or control.]


The one-way ANOVA for this comparison "did not reach traditional significance" (p=.08), but two of the post hoc comparisons did (uncorrected for multiple comparisons involving 16 groups). The p<.09 bar in the figure is in the wrong place. Below is a table I made using the effect size calculator (ESC) for Cohen's d, compared to what was reported in the paper.

The key HERA condition (R/L) did not differ from the control condition, so the predicted hand clenching improvement in memory did not materialize. The superiority of R/L over the other two clenching configurations was due to worse performance in the latter. In other words, if you squeeze a ball with your left hand before encoding, you'll do worse than if you didn't (all statistical objections aside) — and the L clenching before retrieval didn't help. The authors stated otherwise, however:

Individuals who encoded language-based information immediately following right hand clenching (left hemisphere activation), and recalled such information immediately following left hand clenching (right hemisphere activation), demonstrated superior episodic memory compared to the other hand clenching conditions. It is noteworthy that this condition was also superior to the no hand clenching control condition, though not significantly so.

The difference between the two rightmost bars in Fig. 3 above is not terribly close to being significant (as far as I can tell), so the major hypothesis was not supported here.

Clench Your Fist to Get a Grip on Memory? I don't think so.

Thanks to blog commenter Lew for first pointing out this study.

ADDENDUM (May 1, 2013): An Erratum to Figure 3 has been posted in the Comments section of the PLOS ONE article. It might have been in response to my comment in a previous thread, but this comment wasn't addressed directly.

ADDENDUM #2 (May 5, 2013): There has been a formal correction to Figure 3, which can be downloaded here (as a TIF). This doesn't affect any of the other points I made in this post, which were never addressed.


Footnotes

¹ The fist-clenching activation of motor cortex is supposed to spread to dorsolateral prefrontal cortex, or so it goes (Harmon-Jones, 2006).

² @neuromusic noted that the authors measured ear temperatures: "Immediately following pre-clenching condition, participants’ ear temperatures were taken (to be reported elsewhere)..." This sounded a little bizarre, but I found this publication by Propper and Brunyé, Lateralized difference in tympanic membrane temperature: emotion and hemispheric activity, which must explain the concept.

³ @rogierK thought the reported effect sizes were way too large.


References

Habib R, Nyberg L, Tulving E. (2003). Hemispheric asymmetries of memory: the HERA model revisited. Trends Cogn Sci. 7(6):241-245.

Harmon-Jones E. (2006), Unilateral right-hand contractions cause contralateral alpha power suppression and approach motivational affective experience. Psychophysiology 43(6):598-603.

Owen AM. (2003). HERA today, gone tomorrow? Trends Cogn Sci. 7(9):383-384.

Propper, R., McGraw, S., Brunyé, T., & Weiss, M. (2013). Getting a Grip on Memory: Unilateral Hand Clenching Alters Episodic Recall PLoS ONE, 8 (4) DOI: 10.1371/journal.pone.0062474

Tulving E, Kapur S, Craik FI, Moscovitch M, & Houle S (1994). Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proceedings of the National Academy of Sciences of the United States of America, 91 (6), 2016-20 PMID: 8134342

Does Tylenol Exert its Analgesic Effects via the Spinal Cord?

What do we (not) know about how paracetamol (acetaminophen) works? (Toussaint et al., 2010)

. . .
From the beginning, the focus of the search for paracetamol’s analgesic mechanism has concentrated on the central nervous system. When administered intraventricularly [i.e., directly into the ventricular system of the brain], acetaminophen produces no significant analgesia (115, 132). This finding lead to attempts to inject acetaminophen into the spinal cord (i.t.), which produced marked dose-related antinociception (132).

Yesterday’s post about Tylenol as a cure for mortality salience and existential dread got me a little worked up. The first author’s public endorsement of acetaminophen as a possible treatment for chronic anxiety disorders was too much to handle (along with the less than stellar experimental rigor). Is watching a 4 min clip of a David Lynch film really the same thing as a clinically diagnosed psychiatric disorder (Randles et al., 2013)? Why Tylenol and not other pain relievers? What is the hypothesized mechanism of action? Wouldn’t we already know by now, from epidemiological studies at the very least, if Tylenol was an effective anti-anxiety medication?

So I started wondering about acetaminophen's actual mechanism of action. I was quite surprised that it's somewhat mysterious. Randles et al. cited one paper on this:

Second, acetaminophen affects a number of brain regions, some of which are not directly related to physical or social distress (Toussaint et al., 2010).

This led me to believe there was evidence from human neuroimaging studies. Turns out there isn't, beyond the Dewall et al. (2010) paper, which states:

Although the precise mechanisms by which acetaminophen exerts an analgesic effect are still unclear, it is widely accepted that acetaminophen reduces pain through central, rather than peripheral, nervous system mechanisms (Anderson, 2008; H.S. Smith, 2009).

I would like to point out that the spinal cord is part of the central nervous system. So if it's really true that acetaminophen exerts its pain-relieving effects through synapses in the spinal cord, then what does this say about providing relief from the angst of social exclusion, mortality salience, and existential dread? That it's based on nociceptive spinal cord neurons in laminae I, II, and V? For a visual illustration of this pathway, I highly recommend viewing the animation, Dissection of DLF blocks analgesia, at Neuroscience Online.

One hypothesis is that Tylenol (acetaminophen) may act on descending serotonergic pathways (purple projection) at the level of the spinal cord (red synapses). Figure modified from Neuroscience Online.


However, it's not that simple. The review paper by Toussaint et al. (2010) concluded, "No one mechanism has been definitively shown to account for its analgesic activity." For its proposed mechanisms of action, they presented evidence both for and against Cyclooxygenase (EC 1.14.99.1, COX) inhibition, COX-1, COX-2, 'COX-3', peroxidase, nitric oxide synthase, cannabinoid receptors, and of course serotonin:

There is substantial evidence that paracetamol’s mechanism of analgesia in some manner involves the descending serotonergical pathway. 5-HT neurons, largely originating in raphe nuclei located in the brain stem (117, 118) send projections down to the spinal cord that synapse on afferent neurons entering the spinal cord. These descending projections exert an inhibitory (analgesic) effect on the incoming pain signal before it is transmited to higher CNS centres.

Note that these are not the same serotonergic pathways often implicated in depression. The terminal synapses for the latter are indeed located in the brain and not the spinal cord.

Last night, in real life, I followed the Watertown news live via @sethmnookin and @taylordobbs (like many others).

This morning I dreamt that my workplace had transformed into an institutional fortress taken over by a gang of murderous criminals. The actual law enforcement authorities were too busy watching television talk shows to do anything about it. The thugs were threatening and torturing and killing people in the building. I managed to escape down a balcony exit and hid out for a while, avoiding detection but fearful that the thugs would find me and kill me. They were unstoppable, and there seemed to be no way out. I informed an old West-style sheriff, who managed to detain a carload of the evildoers. While continuing to hide, I wondered whether I would be able to shoot them all dead with a fully automatic weapon before they shot and killed me.

Then an early morning doorbell rang and woke me up. It was an unexpected FedEx delivery. In my barely awake state, I thought it might be a bomb.

Why am I telling you all this?? Because I find it very hard to believe that Tylenol, a drug that's relatively ineffective for my own headache pain, could possibly alleviate the anxiety caused by this nightmare. Or by the real life nightmare that's affected so many people in Boston.


References

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.

Randles, D., Heine, S., & Santos, N. (2013). The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats. Psychological Science DOI: 10.1177/0956797612464786

Toussaint, K., Yang, X., Zielinski, M., Reigle, K., Sacavage, S., Nagar, S., & Raffa, R. (2010). What do we (not) know about how paracetamol (acetaminophen) works? Journal of Clinical Pharmacy and Therapeutics, 35 (6), 617-638 DOI: 10.1111/j.1365-2710.2009.01143.x

Existential Dread of Absurd Social Psychology Studies

Scene from Rabbits by David Lynch

“In a nameless city, deluged by a continuous rain, three rabbits live with a fearful mystery.”

The latest "elegant and breathtaking"¹ paper in Psychological Science presents a rather muddled view of film aesthetics, continental philosophy, surrealism, mortality salience, and stigmatizing attitudes towards sex work (Randles et al., 2013). Oh, and how Tylenol® brand acetaminophen can ease the existential dread evoked by all of these modern horrors.

The authors explained the purpose and implications of their study in the APS press release:

According to lead researcher Daniel Randles and colleagues at the University of British Columbia in Canada, the new findings suggest that Tylenol may have more profound psychological effects than previously thought:

“Pain extends beyond tissue damage and hurt feelings, and includes the distress and existential angst we feel when we’re uncertain or have just experienced something surreal. Regardless of the kind of pain, taking Tylenol seems to inhibit the brain signal that says something is wrong.”

Randles and colleagues knew from previous research that when the richness, order, and meaning in life is threatened — with thoughts of death, for instance — people tend to reassert their basic values as a coping mechanism.

The researchers also knew that both physical and social pain — like bumping your head or being ostracized from friends — can be alleviated with acetaminophen. Randles and colleagues speculated that the existentialist suffering we face with thoughts of death might involve similar brain processes. If so, they asked, would it be possible to reduce that suffering with a simple pain medicine?

No!!  I think this is a ridiculous assertion that gets away with using language (and dependent measures) that not only lack precision, but also lack an analogical relation to the real phenomenon under discussion. The leaps of logic were so egregious that I don't know where to begin...

...so let's start with the meaning-maintenance model (MMM) that motivated the work. MMM "posits that any violation of expectations leads to an affective experience that motivates compensatory affirmation" (Randles et al., 2013). Any violation?? So all sorts of psycholinguistics experiments that involve syntactic violations ² will motivate compensatory affirmation? If that's the case, then David Lynch films will often "motivate compensatory affirmation."


But does a David Lynch film “hurt” you?

...Lynch’s films have the ability to “disturb, offend or mystify” (Rodley, 2005, p. 245). Insofar as it “hurts” to watch some of Lynch’s films, as it arguably hurts whenever one is assaulted by thoughts and experiences that are at odds with one’s expectations and values, the question arises as to how this uncomfortable feeling is represented in the brain.

First, David Lynch is one of my favorite directors, and I have never felt "hurt" by watching one of his films. Second, Randles et al. never, at any point in their experiments, address how Lynch-viewing is represented in the brain.

What did the authors actually do? In brief, they asked ~350 young Vancouverites to participate in one of two experiments. In the first study, 121 subjects wrote about death or about dental pain. In the second study, 228 subjects watched a 4 min clip from Rabbits or from The Simpsons. In each case, half of the participants received acetaminophen, half received placebo. Why? What motivated the choice of acetaminophen, as opposed to aspirin, ibuprofen, or naproxen? This was based on a study by Dewall et al. (2010), another problematic paper³ in Psych Sci. There was no mechanistic reason for the original choice.

Here's the neuro-rationale for the current study (Randles et al., 2013):

The present research is predicated on four key findings in the literature: (a) Both physical and social pain are associated with activation in the dACC [dorsal anterior cingulate cortex]⁴ (e.g., Eisenberger et al., 2003), (b) the dACC is activated in response to anomalies (e.g., Botvinick et al., 2004), (c) social rejection can produce the same compensatory affirmation as other meaning threats (e.g., Nash et al., 2011), and (d) acetaminophen has been shown to reduce physical and social pain, as well as activation in the dACC (DeWall et al., 2010). These findings led us to predict that acetaminophen may also inhibit compensatory affirmation following meaning threats.

The acetaminophen group in Dewall et al. (dose of 2,000 mg a day for 3 weeks) did show less dACC activity in response to cyberball exclusion, but they did not report lower hurt feelings in that situation. The treatment administered by Randles et al. was quite different: a single acute dose of 1,000 mg Tylenol-brand acetaminophen (Rapid Release formula) or 1,000 mg sugar placebo, given 30 min before the critical manipulation.

In Exp. 1, writing two paragraphs about what will happen to your body after death was designed to trigger mortality salience, or thoughts about the inevitability of death. This in turn would lead to compensatory affirmation of cultural views. How was this measured? By assessing the severity of punitive attitudes towards women who engage in sex work! This is the worst part of the study, in my opinion.

Social judgment survey

Finally, participants read a hypothetical arrest report about a prostitute and were asked to set the amount of the bail (on a scale from $0 to $999). This measure has been used in a number of other meaning-threat studies (Proulx & Heine, 2008; Proulx et al., 2010; Randles et al., 2011; Rosenblatt, Greenberg, Solomon, Pyszczynski, & Lyon, 1989). Participants are expected to increase the bond amount after experiencing a threat, because trading sex for money is both at odds with commonly held cultural views of relationships and against the law. Increasing the bond assessment provides participants n opportunity to affirm their belief that prostitution is wrong.

The study took place in Vancouver, Canada. What are the laws on prostitution?

In Canada, the buying and selling of sexual services are legal, but most surrounding activities, such as public communication for the purpose of prostitution, brothels and procuring are offences under the law.

What are current attitudes towards prostitution in Canada?

The views of Canadians on prostitution vary greatly according to age and gender, with a large proportion of men and older respondents voicing support for some kind of decriminalization, while most women and younger respondents are not as comfortable with the idea...
. . .

As evidenced in surveys conducted by Angus Reid Public Opinion in 2009 and 2010, only about a quarter of Canadians (22%) are aware that exchanging sex for money is legal in Canada, while seven-in-ten (70%) mistakenly believe that the practice is illegal.
. . .

Still, there is no clear consensus on how some of these guidelines are currently applied. While 36 per cent of respondents believe the Criminal Code provisions related to communication and brothels are fair to the purpose of protecting the public good, almost half (47%) think the rules are unfair and force prostitutes into unsafe situations.

Here are my reactions to the Prostitute-Bail dependent measure:

(1) Yay! Let's stigmatize the prostitute, not the johns!

(2) Does the baseline for these bail judgments differ by sex? age? religion? ethnicity? As professional polling can attest, attitudes vary greatly along demographic lines. The participant pool was quite diverse, and we know nothing about age.

We recruited 121 participants (81 women, 40 men). The sample was predominantly of East Asian (45%), European (29%), and South Asian (12%) descent.

(3) Participants were randomly assigned to one of four groups, but we don't know anything about the randomization  - perhaps the most religious and judgmental people ended up in the mortality salience/placebo condition.

(4) To reiterate, we don't know anything about possible demographic differences in the amount of bail set. And that is the only dependent measure!! We don't know how anyone would allocate money or set a price in another situation that is not "morally laden". Let's say you're selling a used car - what would you charge?

At any rate, the authors reported that the mortality-salience/placebo group punished the "norm violator" by a significantly larger amount than the other three groups, t(112) = 2.33, p = .02, d = 0.52.

Fig. 1 (Randles et al., 2013). Results from Study 1: mean bond value set for the prostitute as a function of group (mortality-salience vs. control condition crossed with placebo vs. acetaminophen condition). The scale ranged from $0 to $999. Error bars represent the standard error for each group.

Moving right along to Exp. 2, we discover that the authors decided to use a different dependent measure for no clearly motivated reason. This makes it impossible to compare the outcome of the salience mortality manipulation to the David Lynch manipulation.

We also changed the dependent measure [in Exp. 2]. This study was conducted 3 to 6 months after a well-publicized local riot that followed the Vancouver Canucks’ loss in their bid for the Stanley Cup, and we expected that most students held a negative view of the riot. Thus, we expected that after a threat, participants would affirm this view by calling for stronger punishment for the rioters. Participants were informed that people were debating whether the rioters should be given sentences more lenient than those for comparable individual acts of vandalism, because the rioters had acted impulsively, or should be given stiffer sentences, because they had taken advantage of the city while it was vulnerable. Participants then marked a spot on a line from 0% to 200%. They were told that 0% indicated that rioters should not be fined, that 100% indicated that rioters should receive a normal fine, and that 200% indicated that rioters should receive a doubled fine.

One initial critique is that the Vancouver hockey riot itself provoked MMM. It was a mob event that people could not explain rationally. The subjects were more likely to have been directly affected by this event (in comparison to the hypothetical sex worker bail), by either knowing someone who participated or who was present, or by witnessing the event live or through social media, or by having a favorite business vandalized. In addition, the assigned fines were relative, not absolute. A 150% fine out of... $100 or $1,000 or $10,000?

At any rate, the authors reported that participants in the Lynch/placebo group wanted to punish the rioters by a significantly larger amount than did participants in the other three groups, t(203) = 2.64 p < .01, d = 0.43.

Fig. 2 (Randles et al., 2013). Results from Study 2: mean preference for the penalty to be given individuals convicted of vandalism or theft during the Vancouver hockey riot as a function of group (threat vs. control condition crossed with placebo vs. acetaminophen condition). The rating scale ranged from 0% (no fine for a conviction), through 100% (a normal fine), to 200% (a doubled penalty).


Collectively, the results were taken as evidence that Tylenol can potentially treat chronic anxiety disorders, a conclusion that filled me with existential dread:

The study demonstrates that existentialist dread is not limited to thinking about death, but might generalize to any scenario that is confusing or surprising — such as an unsettling movie.

“We’re still taken aback that we’ve found that a drug used primarily to alleviate headaches can also make people numb to the worry of thinking about their deaths, or to the uneasiness of watching a surrealist film,” says Randles.

The researchers believe that these studies may have implications for clinical interventions down the road.

“For people who suffer from chronic anxiety, or are overly sensitive to uncertainty, this work may shed some light on what is happening and how their symptoms could be reduced,” Randles concludes.

I have a few final questions for the authors, since this violation of my expectations led to an affective experience that motivated my own compensatory affirmation processes:

• Why wasn't the dose adjusted by weight? A 45 kg woman got the same dose as a 90 kg man. 
• Was physical pain assessed in the subjects pre/post-treatment? No it was not. 
• Did anyone have a headache or any other physical pain before treatment? We don't know... which would be important to know, since relieving physical pain will make you less cranky and irritable. 
• Is there a single neuroimaging study that has administered acetaminophen at the dose and time course used here? No. 
• What is the evidence that acetaminophen affects the hemodynamic response in the same exact dACC region hypothesized to control physical, existential, and social pain? 
• Has there been a single fMRI study in which subjects have watched Rabbits and Simpsons, counterbalanced in a single session while their brains were scanned? 
• What is the Rabbits > Simpsons neural activation pattern? 
• Why wasn't there a measure that the Lynch clip was actually "disturbing" or that the Simpsons clip was enjoyable? Actually, none of the manipulations induced changes in affective state on the PANAS.

To ease my existential dread, it's time to watch Rabbits in its entirety.




Footnotes

¹ Former Psychological Science Editor Robert V. Kial:

At meetings and via email, authors often asked me, “What sort of paper is a good candidate for Psychological Science?” ... And when feeling particularly candid, I might say that the ideal Psychological Science manuscript is difficult to define, but easily recognized — the topic is fundamental to the field, the design is elegant, and the findings are breathtaking.

² For example: "The metal was for refined by the goldsmith who was honored" (Friederici et al., 1996).

³ For a lengthy exposition on the problematic aspects of the Dewall et al. paper, see Suffering from the pain of social rejection? Feel better with TYLENOL®.

⁴ At the risk of sounding like a broken record, the dACC has been associated with a wide array of cognitive and emotional control functions (Posner et al., 2007). In the TYLENOL® post, I said:

The "shared neurobiological systems" [for social and physical pain] are thought to be located in the dorsal anterior cingulate cortex (ACC), a brain structure that contains discrete regions responsive to physical pain (Kwan et al., 2000). Interestingly, externally applied vs. self-administered thermal pain activate anatomically distinct areas of the ACC (Mohr et al., 2005). Furthermore, it is not at all clear whether the same regions of ACC represent social pain and the affective components of physical pain. In a study designed to dissociate expectancy violations from social rejection, the dorsal ACC was activated when expectations were violated, while ventral ACC (quite distant from the physical pain regions) was activated by social rejection (Somerville et al., 2006).

References

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.

Randles, D., Heine, S., & Santos, N. (2013). The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats Psychological Science DOI: 10.1177/0956797612464786


Further Reading on Surrealism, Dread, and Tylenol:

Surrealistic Imaging Experiment #1

Of Mice and Women: Animal Models of Desire, Dread, and Despair

Suffering from the pain of social rejection? Feel better with TYLENOL®