Psychosomatic contributors to Long Covid suffering

“Some people are willing to ‘feel sorry for the sufferers’ if we find a traditional pathogenic mechanism … and that, to me, seems a fundamentally flawed point.” - Alan Carson

“Lots of people act like psychosomatic = not a real problem. Unfortunately, having a symptom for psychosomatic reasons sucks just as much as having it for any other reason. Sometimes it sucks more, because nobody takes you seriously.” - Scott Alexander

“Psychosomatic” to many people implies “caused by anxiety or stress”. However medical professionals, especially in the UK, use the term much more generally to simply mean that symptoms are caused by something in the central nervous system, rather than something happening elsewhere in the body.¹ This is the usage I will use here. To make the definition a bit more precise, in psychosomatic illness there is is no gross tissue abnormality that would be visible on a brain scan. So, a brain tumor would not be psychosomatic although it is an abnormality in the central nervous system.

Are all “psychosomatic” diseases are “psychological”? Well, it depends what you mean by “psychological” - the boundaries between psychology and neurology are blurry. Generally speaking however, psychological illnesses are a subset of psychosomatic ones.

With the exception of an op-ed in The Wall Street Journal and a major piece in The New Republic, psychosomatic causes for Long COVID have received relatively little attention in the popular press. Also, mention of possible psychosomatic contributors tends to elicit a very negative reaction on social media. There are a number of reasons for this:

First, some people think the psychosomatic label implies they are imagining their symptoms or making them up. This is wrong — in psychosomatic illnesses, the symptoms are real. In some cases the brain may cause physical changes within the body which cause the symptoms. In other cases the brain may misjudge signals from the body as being due to bodily harm, amplifying them and rendering them as pain in conscious awareness. In both cases the symptoms and the suffering they cause are completely real and can’t simply be avoided by “thinking your way out of them”.

Secondly, some people have trouble grasping psychosomatic illness due to dualistic thinking. Due to centuries of religion, people conceptualize the “mind” as completely separate from the body. Either implicitly or explicitly they conceptualize the mind and body as made of separate material. However modern science rejects this view, viewing the mind as arising from the brain which is biological tissue just like the rest of the body. The brain’s peripheral nervous system has neurons which connect deeply to every tissue of your body. The brain controls all our muscles, heart rate, breathing, digestion, body temperature, and even some aspects of our immune system such as inflammation.² The brain decides how fatigued we feel, how much pain or comfort we experience, and how calm or agitated we are. There is no bodily symptom that cannot in principle be generated solely within the central nervous system.

Thirdly, people worry that discussions of psychosomatic causes could lead to delays in patients going to a doctor to get treatment for underlying physical illness. However, as Horn et al. point out, the reverse is also true.³ Patients who are not aware of psychosomatic causes will likely go to a medical doctor instead of a therapist, psychiatrist, or neurologist. They will undergo expensive workups and wild goose chases, delaying appropriate care. In the meantime, they waste valuable healthcare resources. Due to the media’s focus on possible physical causes of Long Covid, and the general lack of understanding of the nature of psychosomatic causes, I suspect more people with Long Covid symptoms are going to their doctor’s office rather than to a therapist or psychiatrist, who would be better equipped to handle psychosomatic issues. In my experience talking with several people with Long Covid, psychosomatic causes are not even on their radar. Recognizing the psychosomatic contributors to one’s illness can bring relief as many psychosomatic causes have established treatments, as I’ll discuss in a further post. Another point is that many Long Covid sufferers are taking many supplements which are not evidence-based, in a desperate attempt to treat what they perceive as a biological illness. For instance, large numbers of Long Covid patients take benadryl, based on a few case reports and coverage of this treatment in the popular press. While benadryl before bed can help with sleep, tolerance quickly develops. Benadryl is not safe to take long term and causes fatigue and cognitive dysfunction. Another popular treatment, niagen, has a bit of evidence to support its use but can induce insomnia. Curcumin and piperine (which are often sold together) have no rigorous science supporting them for any medical use and may cause problematic drug-drug interactions. A massive alternative medicine industry has arisen to fleece Long Covid patients with unproven, expensive, and dangerous treatments, including blood “washing”, ivermectin, hyperbaric oxygen, and antibody infusions that can cost thousands each. One of the most concerning treatments comes from clinics which sell mesenchymal stem cell injections. Stem cell clinics are not regulated much by the FDA and currently hawk stem cells as cures for dozens of different conditions. In addition to costing thousands of dollars, stem cell treatments carry risk of severe harm including infection, disability, and death.

The situation here highlights the problems caused by having our medical system split into two completely separate systems - one for “physical illnesses” (your doctor’s office or emergency room) and one for “mental illnesses” (your therapist or psychiatrist’s office). Unfortunately, your average doctor isn’t trained to diagnose and treat psychosomatic illnesses. Doctors diagnose stuff primarily through tests, and we lack good diagnostic tools for probing the brain - this is why depression, anxiety, and other mental illnesses are not diagnosed by scans or blood tests. Often if doctors can’t find anything wrong via testing, they may assume the patient is feigning illness or dismiss the patient as being overly hysterical. The patient will leave feeling gaslit and

Finally - fear of attacks from the CFS/ME community. I believe some medical professionals are afraid to talk about psychosomatic factors publicly due to a history of bullying and attacks from people in the chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) community. Many of these people are very wedded to the idea that CFS/ME is always a purely biological illness which they will only be able to recover from when a biological cure is found. However, the reality is that despite decades of research, no consistent biological abnormalities have been established for patients with CFS/ME. (Note: I’m in favor of doing more research, but let’s face this reality. Likely CFS/ME is not one thing but rather a cluster of symptoms (syndrome) with many different causes. ) There are numerous stories of people making full recoveries from CFS/ME using psychological techniques. Many CFS/ME sufferers view Long Covid as form of CFS/ME and hope that interest in Long Covid will lead to more funding to find a cure for CFS/ME. Randomized controlled trials show that cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are at least somewhat helpful for patients with mild to moderate CFS/ME (see my discussion here). CBT and GET can be theoretically justified by psychosomatic and “bio-psycho-social” theories for CFS/ME. A 2011 article in the British Medical Journal describes how doctors who did research on CBT treatments for CFS/ME have suffered harassment. The article also describes how in 2009 a paper in Science claimed that CFS/ME was caused by the XMRV retrovirus. At least 10 follow-up studies failed to replicate that research, and the researchers who did those replication attempts found themselves also the subject of harassment. An advisor to the ME association is quoted as saying that it is a tiny fraction of the CFS/ME community who engage in this harassment, “perhaps 50 to 100 people”. Still, 50 - 100 people (who are likely unemployed and lots of free time) can wreak a lot of havoc online. UK psychiatrist Simon Wessely has claimed he suffered death threats. A more recent 2021 article in the British Medical Journal has described how doctors have been attacked for talking about how anxiety about exercise can perpetuate CFS/ME. Finally, Paul Garner, a UK medical doctor who led the Cochran infectious disease group, has received death threats for speaking about how he used exercise and psychological techniques to recover from Long Covid. He describes it as a “form of bullying to shut me up”.

General findings

A September 7, 2022 study of nurses (96.6% female, 96.5% white) published in JAMA Psychiatry found that “depression, anxiety, perceived stress, loneliness, and worry about COVID-19 were prospectively associated with a 1.3- to 1.5-fold increased risk of self-reported post–COVID-19 conditions”. It's worth noting, though, that 40% of the Long Covid patients in the study did not have any sources of psychological distress before Covid. Another prospective study from the UK found similar results. There are also many uncontrolled-cohort studies and some retrospective studies reporting high rates of anxiety, depression, and insomnia amongst Covid-19 patients, but I am not going to summarize them since they are uncontrolled and some of those studies suffer from response bias and other issues. A 2021 study in JAMA Internal Medicine analyzed patients early in the pandemic (May - Nov 2020) found that about 50% of people reporting at least one Long Covid symptom had a negative antibody test. It’s not at all clear how to interpret this finding, and the study may have some methodological issues, as Zvi discusses at great length.

Psychosomatic causes to consider

“False fatigue alarms” / functional neurological disorder

This is probably the most important one! I have an entirely separate post on it - please read it! In brief, the idea here is that there are wiring issues in subconscious parts of the brain which generate the feeling of fatigue. This might possibly be considered a type of functional neurological disorder.

Depression

The fact depression can cause somatic symptoms is reflected in the widely used Hamilton depression rating scale (“HAM-D”). The list of symptoms that are commonly caused by depression is quite long:

I admit, this is pretty weird, but this is a well established finding in psychology, even though the cause for these symptoms remains somewhat mysterious. It’s worth mentioning that depression is associated with higher levels of systemic inflammation, although the direction of causation isn’t very well understood (it seems to be bidirectional). Another thing you can observe from the HAM-D is that people with depression are also likely to have hypochondriasis, or preoccupation with their physical health. This can lead to somatic symptom disorder (see below).

As a point of comparison, if we look at a different depression screening inventory, the QIDS-SR, we don’t find any items related to somatic symptoms, but we do find two items related to fatigue (items 14 and 15).

Insomnia

One study found that poor sleep quality in the month before Covid increases the odds of developing Long Covid by 3.5 times.⁴ Patients who had sleep difficulties were 50% more likely to have difficulties with mobility and three times as likely to report cognitive problems. A 2022 study from the Cleveland Clinic found that more than 40% of patients with Long COVID reported sleep disturbances.⁵ This study was not controlled, however. A study with a control group found that insomnia was ~80% more common among patients who had either moderate or severe Covid, compared to controls, but not more common among those with mild or asymptomatic Covid.⁶ A survey of 2,980 adults found, not unsurprisingly, that patients with Covid and insomnia reported longer illness than those without insomnia. A study of the Veterans Administration databases found that “sleep-wake disorder” was the 3rd most common medical problem associated with Covid-19 infection in medical records with a whopping hazard ratio of 14.53.⁷

There is mixed research on whether people with chronic fatigue syndrome, a condition similar to Long Covid, are more likely to have sleep issues.

I believe my Long Covid experience may have been partially triggered by insomnia I developed about five weeks after getting Covid. The insomnia was the worst I have ever experienced, by far, and lasted all through August 2022. Because I was so fatigued from both Covid and insomnia, I was barely doing anything during the day and was napping a lot. This made the insomnia worse because I wasn’t building up a proper sleep drive. This sort of vicious cycle, at least anecdotally, appears to be not uncommon among Long Covid patients. The effects of chronically reduced sleep are numerous and include fatigue, muscle aches, immune dysfunction, and cognitive problems. If you just get poor sleep for just a day or two, the body recovers by sleeping more subsequent nights. Unfortunately, research shows that insomnia that lasts more than a week is much harder to recover from because the mechanism for compensatory "catch-up" sleep breaks down.

Anxiety

“It’s never been the case that you can get an asymptomatic respiratory virus and your brain will shrink. And if it is shrinking, I worry it’s shrinking when you’re reading the paper about your brain shrinking, and not actually from the virus”. — Vinay Prasad, MD

Having Long Covid is extremely stressful and anxiety-provoking. There has been intense scare-mongering in the news media about Long Covid, suggesting that it can lead to lifelong uncurable CFS/ME or that it can shrink your brain. Increased anxiety and sympathetic activity can cause increased heart rate, increased body temperature, impaired digestion, sweating, faster and shallower breathing, impaired sexual function, trembling or shaking, brain fog, cognitive dysfunction, headaches, and fatigue. The drug guanfacine, which reduces sympathetic activation, has been shown to help relieve brain fog and cognitive problems in Long Covid patients.⁸

Somatic symptom disorder

“The diagnoses of somatic symptom disorder or related disorders are often delayed, after patients have received inappropriate and excessive ‘diagnosis’ testing, dangerous or ineffective therapies, and multiple, often unnecessary, referrals.” - Horn et al. in “Somatic symptom disorders and long COVID: A critical but overlooked topic”

Somatic symptom disorder is a pretty broad diagnostic category. One common aspect of somatic symptom disorders is that the brain becomes hyper-fixated on sensations in the body. It appears that obsessive focus on bodily sensations can lead to magnification of those sensations and for the brain to start rendering them as pain. Also, when patients are constantly worrying about and attending to sensations in their body, this can lead to cognitive issues, if for no other reason than the obsessive thoughts and sensations crowd out normal thought. As with FND, patients with somatic symptom disorder are often dismissed as feigning or malingering and gaslit and stigmitized by doctors. According to one study on 50 Long Covid patients, 64% met the diagnostic criteria for somatic symptom disorder.⁹

Feedback loops and interactions

There are interactions between all of these. Here’s a diagram I made last October while I was sick with Long Covid that captures the complexity of what may happen in Long Covid. Due to the condition I was in, it took me about three days to make this:

Some key feedback loops are highlighted in yellow. The three biggest feedback loops I observed personally are:

• fatigue making it harder to be active during the day leading to poorer sleep, which leads to more fatigue

• fatigue limiting ability to write/be productive and go to social events, which leads to depression, which leads to more fatigue.

• insomnia causing anxiety about sleep, which causes more insomnia

Interestingly, cognitive behavioural therapy for chronic fatigue syndrome deals directly with these sort of complex interactions between bodily symptoms, thoughts, feelings, and behaviors:

CBT conceptualization of processes that drive chronic fatigue in CFS/ME. From here.

Finally, here is an overview of the “vicious cycle of fatigue” described in the CBT manual for chronic fatigue syndrome (CFS) used in the PACE RCT study, which showed at least some statistically significant benefit for CBT on patients with CFS. Everyone’s case is different but this diagram rings true for me, personally.

Appendix - my Long Covid story, in brief

There are many who doubt the reality of Long Covid. On the other side of the spectrum there are those who think that Long Covid is a lifelong condition for which there is no known cure.  

I was reluctant to publish this because I’m not looking for sympathy and I feel there’s a general stigma against people who write about their illness. Here’s the main points I’m hoping to communicate by publishing this:

• I’m not in denial that Long Covid is a real and serious condition. It was real — I experienced myself. I was severely ill for five months, during which I was unable to work and suffered very greatly.

• The fatigue I experienced was not just from depression, it was much more intense, physical fatigue. Sleep issues and the low dose Remeron I started on month three may have contributed to my fatigue, but I’m not sure how much.

• I recovered fully after 8 months. 

• I used cognitive behavioral therapy and graded exercise therapy methods and I believe they helped. These methods need to be applied with care, but I believe they can help at least a subset of some Long Covid sufferers.

Here’s the summary:

I got Covid at the end of June and had a pretty normal case. A month later, I still had a lot of fatigue and couldn’t work, exercise, or walk more than a few blocks. Despite that, I went on a ten day trip to the SF Bay Area. I developed extreme insomnia on the trip which persisted through August along with extreme fatigue, constant tinnitus, and intense chest pain. During August I only slept 3-5 hours a night except for maybe 1-2 nights. Trazodone did nothing to help with the insomnia, even though it had cured insomnia I had in 2019 overnight. After trying higher doses of trazodone, CBT-i, ambien, and doxylamine, I started sleeping more consistently after starting low-dose remeron. I cured the chest pain by taking very aggressive amounts of Alleve. As a result of my illness I barely did any work at my job in July and August, and went on sick leave in September. I was on sick leave for three months, and during that time I was profoundly fatigued and couldn’t walk more than a mile without being completely exhausted. If I tried to run, my legs would give out immediately and become achy. I was unable to write on my blog or do any cognitively demanding work and became at least low grade depressed. As a result of reading stuff online I developed anxiety around over-exertion and was afraid that I was developing CFS/ME.

In October, as a result of reading Paul Garner’s writings and talking with my psychiatrist I started to re-conceptualize the illness I was experiencing as largely psychosomatic in nature. I stopped reading about Long Covid, stopped my obsessive tracking and thinking about symptoms, and started graded exercise therapy. I got into a Long Covid clinic, which sent me materials from a CFS/ME organization, which I promptly ignored. Over the next two months, through many fits and starts, I slowly built my strength up to the point where I could walk 1-2 miles each day consistently and work maybe two hours a day in December.  The recovery was extremely slow and not linear - there were many days, perhaps 2-3 days a week, where I ended up completely crashed and nonfunctional. During these days I was completely couch-bound and often didn’t leave my apartement. I noticed these “crash” days usually usually came after not sleeping as well. Whether those “crash” days were due to post-exertional malaise, I am not sure, but I tend to think they were more linked to my sleep quality and a classic insomnia cycle (good sleep being followed by poor sleep etc). Eventually, my system started to stabilize in January. I returned to something similar to my pre-covid exercise routine, running and weightlifting a few times a week, although at a greatly reduced level. I went off Remeron. Then, in mid-January I developed bad insomnia again which lasted about 5 - 6 weeks. My condition regressed greatly. Once I got my sleep straightened out, I started to return to normal. Today (early April) I consider myself mostly recovered. I walk about a mile or so every day and run 1-2 times a week. I can only run 1-2 miles, as opposed to the 4-5 mile runs I was doing pre-covid, but I am slowly building back to my pre-covid strength. I am taking medication for sleep still but slowly tapering off. A few days a week I end up very fatigued and crashed but overall I am doing much better.

Appendix - non psychosomatic contributors

This post is specifically on psychosomatic contributors. However, since I know I will be attacked for ignoring biological contributors, I want to discuss “biological” contributors a bit here. To be clear, I’m talking about stuff happening in the body that is causing symptoms at the 3+ month mark. Obviously, people who had severe Covid-19 are likely to have organ damage, especially in their heart and lungs, which may be permanent or take months to heal. Such patients may also have persistent micro-clots. A lot of Long Covid research and speculation revolves around persistent immune system deregulation. I have looked at some of the research on this a bit and found the picture very unclear. To the extent there are weird things going on with the immune system, a lot of the study authors point out this may be due to persistant SARS-CoV-2 virus or latent virus reactivation (see below). Another theory revolves around mitochondrial damage, but more work is needed before we can say anything definitive. The “niacin deficiency” theory promoted by Gez Medinger I find very unconvincing. (That said, niacin is a very safe supplement that can boost energy and tamper neuroinflammation so may be worth trying). There is no scientific evidence that Long Covid is caused by excess histamine or that taking anti-histamines helps with Long Covid.

Persistent SARS-CoV-2 virus

As far as persistent virus, I’m pretty convinced this may be thing in some patients, although there isn’t a lot of hard evidence for it. In other viral illnesses it has been observed that some viruses evade the immune system by “de-evolving” to a much slower-replicating form, and something like that could be happening in some Covid patients. A lot of people point to autopsy studies here, which show lingering bits of viral protein or viral RNA in some patients months after they got Covid. However, it’s not clear if the amounts of virus found in autopsy studies are clinically significant. One of the autopsy studies specifically highlights that the people with persistent virus had ‘seemingly recovered” - ie they were not reporting symptoms before they died. Another study found that 4% of patients who had Covid-19 shed fecal viral RNA seven months after diagnosis. They found that within the first 28 days fecal RNA was associated with a higher incidence of gastrointestinal symptoms. Non-randomized and non-blinded observational studies show about ~20 - 30 % of Long Covid patients find a booster shot is helpful, and this may be because it ramps up immune response which flushes out persistent virus. Some case reports find that anti-viral drugs like Paxlovid can help Long Covid patients. Again, this may be because those drugs flush out persistent virus.

Latent virus reactivation (in particular Epstein-Barr virus)

I personally suspect I had this, in August 2022. Unlike the other purported biological causes for Long Covid I am fairly (80%) convinced this is a real and important contributor. Here are some papers with key quotes in bold:

“Observational study of 240 Covid patients: “Serological evidence suggests recent EBV reactivation (early antigen–diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12).”

Peluso, Michael J., et al. “Chronic Viral Coinfections Differentially Affect the Likelihood of Developing Long COVID.” Journal of Clinical Investigation, vol. 133, no. 3, Feb. 2023, p. e163669.

“66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse IgG or EBV viral capsid antigen IgM.”

Gold, Jeffrey E., et al. “Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation.” Pathogens, vol. 10, no. 6, June 2021, p. 763.

Observational study of 34 patients: “EBV reactivation is associated with longer ICU length-of-stay.”

Simonnet, A., et al. “High Incidence of Epstein–Barr Virus, Cytomegalovirus, and Human-Herpes Virus-6 Reactivations in Critically Ill Patients with COVID-19.” Infectious Diseases Now, vol. 51, no. 3, May 2021, pp. 296–99.

Another observational study of 67 patients: “We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.”

Chen, Ting, et al. “Positive Epstein–Barr Virus Detection in Coronavirus Disease 2019 (COVID-19) Patients.” Scientific Reports, vol. 11, no. 1, May 2021, p. 10902.

Study of 30 Long Covid patients compared to 20 age and gender matched controls: “SARS‐CoV‐2 persistence could not be detected in our study participants up to 10 weeks after infection, but EBV reactivation in the throat was more common in patients with Long‐COVID fatigue, also months after acute SARS‐CoV‐2 infection, compared with convalescent SARS‐CoV‐2 patients.”

Rohrhofer, Johanna, et al. “Association between Epstein‐Barr‐Virus Reactivation and Development of Long‐ COVID Fatigue.” Allergy, vol. 78, no. 1, Jan. 2023, pp. 297–99.

“reactivation of latent EBV and SARS-CoV-2 RNAemia at T1 are factors that anticipate, to varying degrees, PASC at T3”

Su, Yapeng, et al. “Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae.” Cell, vol. 185, no. 5, Mar. 2022, pp. 881-895.e20.

“.. unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus.”

Klein, Jon, et al. Distinguishing Features of Long COVID Identified through Immune Profiling. medrXiv preprint, 10 Aug. 2022.

References

1. I got this definition from a very smart UK medical doctor named Eliot Nicholson. He has an excellent YouTube series on psychosomatic illness and mentions how the term is treated a bit differently in the UK. Merriam-Webster defines it as “of, relating to, or being symptoms of the body that are caused by disturbances (as stress) originating in the mind”, which is nearly the same except using “mind” instead of “brain”. Oxford’s first definition is overly narrow (in my opinion), defining it as “caused by stress and worry, rather than by a physical problem such as an infection”. Oxford’s 2nd definition is “connected with the relationship between the mind and the body”, which captures the more general usage of the term.

2. Koren, Tamar, et al. “Insular Cortex Neurons Encode and Retrieve Specific Immune Responses.” Cell, vol. 184, no. 24, Nov. 2021, pp. 5902-5915.e17.

3. Horn, Mathilde, et al. “Somatic Symptom Disorders and Long COVID: A Critical but Overlooked Topic.” General Hospital Psychiatry, vol. 72, Sept. 2021, pp. 149–50.

4. Paul, Elise, and Daisy Fancourt. “Health Behaviours the Month Prior to COVID-19 Infection and the Development of Self-Reported Long COVID and Specific Long COVID Symptoms: A Longitudinal Analysis of 1581 UK Adults.” BMC Public Health, vol. 22, no. 1, Sept. 2022, p. 1716.

5. Pena-Orbea, Cinthya, et al. “Sleep Disturbance Severity and Correlates in Post-Acute Sequelae of COVID-19 (PASC).” Journal of General Internal Medicine, Apr. 2023.

6. Merikanto, Ilona, et al. “Sleep Symptoms Are Essential Features of Long‐ COVID – Comparing Healthy Controls with COVID ‐19 Cases of Different Severity in the International COVID Sleep Study ( ICOSS‐II ).” Journal of Sleep Research, vol. 32, no. 1, Feb. 2023.

7. Al-Aly, Ziyad, et al. “High-Dimensional Characterization of Post-Acute Sequelae of COVID-19.” Nature, vol. 594, no. 7862, June 2021, pp. 259–64.

8. Fesharaki-Zadeh, Arman, et al. “Clinical Experience with the Α2A-Adrenoceptor Agonist, Guanfacine, and N-Acetylcysteine for the Treatment of Cognitive Deficits in ‘Long-COVID19.’” Neuroimmunology Reports, vol. 3, 2023, p. 100154.

9. Kachaner, Alexandra, et al. “Somatic Symptom Disorder in Patients with Post-COVID-19 Neurological Symptoms: A Preliminary Report from the Somatic Study (Somatic Symptom Disorder Triggered by COVID-19 ).” Journal of Neurology, Neurosurgery & Psychiatry, vol. 93, no. 11, Nov. 2022, pp. 1174–80.