The Joy of Basketball – And What Is Humanly Possible…..

 

In addition to the clinical work – psychiatrists need to have their finger on the pulse of popular culture.  Not just the content – but the process of it all.  How else can you talk with a young patient who is describing their experience of a rock and roll lyric and what it means for their life?  Or patients who are caught up in the latest cultural movements – whether they are useful or not.  Sports of course are a big part of the culture and in the last few months there has been no bigger sports phenomenon than Caitlin Clark of the Iowa Hawkeyes basketball team.  As I type this – she and her teammates are scheduled to appear in the NCAA Women’s Basketball Championship tomorrow afternoon. 

If you are just catching up that is a small part of the story. The statistics leading up to this game are readily available elsewhere and I will just mention a few highpoints without specific numbers.  Clark is the all-time leading scorer for men and women who have played NCAA basketball. The Iowa team has set both live attendance records and records for television viewers - as the most watched basketball game in the history of ESPN and the second most watched non-football event on that network. With that demand the tickets prices for games have also increased greatly sparking new enthusiasm for the viability of women’s sports at all levels. 

What is it about this player and her team that have cause all this excitement? I preface this by saying that I am not a big basketball fan.  I played it in intramural sports and for two years I was one of the statisticians for my high school team.  I have never followed any team consistently but have usually seen the US Olympic teams and a lot of clips of the great players from the NBA. NBA players clearly have a high degree of athleticism and much greater than usual height and physical stature. I recently learned that if you are over 7 feet tall - one person in 6 plays in the NBA.  My maximum height as an adult was 5’10”.  At that height only 0.117% of men play in the NBA.  Currently only 2 of 560 total players in the NBA are 5’9” or less.

The average height in NCAA women’s basketball is quoted between 5’8” and 6’1” by various sources although there are some very tall players ranging from 6’5” to 6’7”.  Caitlin Clark is 6’0” and the team range in height is 5’9” to 6’2”.  Watching Iowa and their closely matched competitors play – physical size fades into the background.  They obviously have the form and the skillset of accomplished basketball players.  I watched NBA star Steph Curry comment on Clark that she is more than just a shooter – she has an excellent ground game.  Seeing clips from her high school games – she had it back then.

There will be the invariable comparisons between men and women.  About how Clark could “never play in the NBA.”  That misses a huge point – there are highly accomplished woman athletes that are every bit as skilled as men.  As an observer of mostly individual sports – it doesn’t take much critical ability to realize that you will never be able to skate like Bonnie Blair, or ski like Lindsey Vonn, or play tennis like Serena Williams, or swim as fast as Katie Ledecky.  More than that you can learn something from watching them.  As a speedskater – I read everything I could find that was written by Bonnie Blair on training. I had the same thoughts about Caitlin Clark describing her jump shot and the left hand component consisting of a thumb flick maneuver.  If you watch her videos, it is so fast it is barely noticeable.  Even as an old man I want to try it. I can imagine that there are boys out there thinking the same thing and wanting to learn how to handle the ball like her.  Like everything else in the world – whether academics or sports – women add greatly to it and that recognition needs to be automatic rather than qualified. People should not give it a second thought.  It is not a “battle of the sexes” and it never has been.

The greats in any field are more than just technically competent.  They set a bar that encourages everyone else.  People start thinking: "That is not something I can do – but I am going to try it." Clark, her coach, and her teammates all consistently say this in post-game press conferences.  There is the realization that an inspirational teammate makes everybody better and that the team is more than just one person no matter how good they are.

What about the average person who has no sporting aspirations? There is a team loyalty factor.  But beyond that – it is inspirational from the standpoint of being a member of the human race. To watch someone accomplish something that nobody has done or done as well before.  Back in the early days of this blog – I posted a link to a video clip that I thought was a good explanation. It involves seeing someone perform so well that it feels uplifting. I get that feeling watching Caitlin Clark ball handling and shooting from well outside of the 3 point line.

The current state of women’s collegiate basketball as well as the abundance of great women athletes is also a reminder that 40 to 50 years ago things were not this good. They were not even close.  I was a high school athlete at that time. Most women’s basketball teams were intramural. Almost all of the high school resources were focused on boy’s football, hockey, basketball, wrestling, and baseball.  In 1972, two female high school athletes who were highly competitive in tennis, running, and cross-country skiing sued to be able to compete in those programs at their high schools. Since there were no programs available for girls – they sued to participate in the boys’ program.  Judge Miles Lord in a landmark ruling (1) concluded that they should be allowed to compete in those programs and compete with boys because discrimination in sports programs solely based on sex was a violation of the 14^th Amendment. He was backed up in appeal by the Eighth Circuit Court of Appeals (2). This ruling led to the development of far more resources for girls’ and women’s’ athletic programs than were previously possible. This ruling illustrates that when given the resources it leads to the development of the expected high caliber of competition and athletes. 

Are there any downsides to these developments?  I do not see any.  As a physician I have seen women athletes with significant and disabling injuries from both contact and non-contact sports.  Anyone watching the current basketball competition realizes that contact and injury can occur even during a game that is considered a non-contact sport. Judge Lord initially emphasized the availability of non-contact sports but today the question comes down to whether girls and women should be able to choose to risk injury by participating in the same way that boys and men do.  I cannot think of a reason why they should not have that freedom of choice. 

There has been criticism for trash talking, posturing on the court, and the usual differences of opinion about what players say in post-game press conferences. I have not seen any behavior to the level of what men's teams have been doing for decades.

I wish Caitlin Clark and all her teammates a great game tomorrow. I have the same wish for their opponents.  If I tune in and sit back to watch great basketball – I will be thinking:  “This is what happens when women have the chance to develop and compete in any field.” 

I am glad I lived to see it….

 

George Dawson, MD, DFAPA

NCAA Woman’s Basketball Postscript -

I watched the last half of the game yesterday. I am not a basketball analyst so I will not give my impressions of what happened.  It is likely if you are reading this that you have heard numerous opinions about this from friends, family, and coworkers. I first noted detailed post-game analyses at the hospital where I used to work. Every day after rounds I would take a break and walk down to the coffee shop for my usual tea or mocha. If it was a Monday – it was a safe bet that I would hear a detailed analysis of the Sunday football game by staff members of multiple disciplines. In some cases, it would involve criticism of the coaching staff, suggestions about who should be drafted, and of course criticism of players.

The post-game comments of the coaches and players of the South Carolina-Iowa game had none of that.  In fact, some of the commentary was the most enlightened commentary about organized team sports that I have seen anywhere. And it was all presented matter-of-fact – no gnashing of teeth or excessive self-criticism and sadness.  Several themes were apparent.

First, the importance of the coaches both on and off the court. Both sets of players emphasized good relationships with the coaches.  They were described as maternal figures and women who had done a lot for the game of basketball.  Both coaches in their Q&A emphasized their interest in growing the game and making sure their players got a lot of out the game besides winning. They emphasized developing a culture where the players know what to say to players, where everyone feels supported and in the case of Coach Staley – where there is extended family involvement. She emphasized recruiting players who had respect for their parents, how those parents had access to the coaching staff, and how both were focused on players succeeding.

Second, confidence at the player level was an important point. The coaches and players talked about it  - how it is instilled and how it develops. It was described as a significant factor is being able to compete irrespective of statistics and related concerns.  Coach Bluder pointed out how Clark came in to their program confident that they could get into the Final Four and despite the naysayers was able to convince everyone that she was correct. 

Third, respect was a frequently used word.  Respect for coaches, teammates, opponents, and fans was an important part of the equation. Numerous examples were given at all levels including previous players who advanced women’s basketball.

Finally, there was an overall plan and formula. This was probably best elaborated by coach Staley who emphasized that the staff who worked with her in implementing these plans were extremely important in the overall success of the team.   

 All things considered NCAA woman’s basketball is an impressive sport no matter what way you analyze it.  Women clearly know how to play basketball.  They know how to win and they know how to lose.  They know exactly where basketball is in the scheme of things.

We can all learn a valuable lesson from that…

 

George Dawson, MD, DFAPA 

 

References:

South Carolina National Championship Postgame Press Conference - 2024 NCAA Tournament  https://www.youtube.com/watch?v=tULkNrlqkI8

Iowa National Championship Postgame Press Conference - 2024 NCAA Tournament  https://www.youtube.com/watch?v=NE6rI8Dkcvw

 

References:

 1:  Judge Lord ordering a school district to allow high school girls to compete on boys' sports teams: Brenden v. Ind. School Dist. 742, 342 F.Supp 1224 (D. Minn. 1972).

The District Court,

“Miles W. Lord, J., held that where plaintiff high school girls wished to take part in interscholastic boys' athletics in tennis in one instance and in cross country and cross-country skiing in second instance and it was shown that plaintiffs could compete effectively on those teams and there were no alternative competitive programs sponsored by their schools which would provide an equal opportunity for competition for female plaintiffs, application of rule prohibiting girls from participating in boys' interscholastic athletic program as to plaintiffs was arbitrary and unreasonable, in violation of the equal protection clause of the Fourteenth Amendment, and application of rules as to plaintiffs could not stand.”

https://www.upress.umn.edu/book-division/images/other-images/equality-for-women-in-high-school-sports_1

 

2:  Eighth Circuit affirming Judge Lord: Brenden v. Ind. School Dist. 742, 477 F.2d 1292 (8th Cir. 1973).

“The Court of Appeals,· Heaney, Circuit · Judge, held that where · high schools attended by plaintiffs, two female students, provided teams for males in noncontact sports - of tennis. – and cross country skiing and running but did not provide such teams for females and where . plaintiffs were - qualified to compete with· boys in such sports, application  of rule -prohibiting females from participating in the boys' interscholastic athletic program as to plaintiffs was arbitrary and unreasonable and in violation of equal protection clause of Fourteenth Amendment. · Affirmed.”

https://www.upress.umn.edu/book-division/images/other-images/equality-for-women-in-high-school-sports_2

Graphics Credit:  Click directly on the photo for the Wikimedia Commons page.  Details from that page include:

John Mac, CC BY-SA 2.0 Caitlin Clark three-pointer (cropped).

Book Reviews on this Blog…..

 

 

Receiving a novel to review this morning reminded me that I should probably comment on that process.  I am very grateful to any authors, editors, or publishers who send papers, books, and book chapters my way.  I have a rigorous reading schedule – especially post-retirement.  Scientific papers are my top priority and I generally read 4 or 5 a day.  That number can go way up if I am working on a specific blog post that requires it.

I rarely read fiction but it all depends on what I am focused on.  For example, the question of suffering came up and I am fortunate to have brilliant friends who are not averse to considering these questions.  One of them sent me Sylvain Tesson’s The Consolations of the Forest – Alone In A Cabin on the Siberian Taiga.  I am halfway through that at this point. I have also read technical texts on rhetoric, philosophy, pollical science, anthropology, and history all in support of the blog.  I consider basic science texts like the medical school courses to all be relevant and will even reach back to my undergrad biology and chemistry majors for reading material. 

My preferred reading is what I consider to be detailed and hopefully innovative work in psychiatry.  To that end I would really like to see the following:

1:  A detailed text on the history of psychiatry.  Every current text that I have seen has major deficiencies.

2:  A detailed text on the evolution of psychiatric hypotheses about mental illnesses and why they never seem to be resolved.  The closest I have come to some answer to that question is from the work of theoretical physicist Sabine Hossenfelder and the idea that there are many mathematical hypotheses about the creation of the universe that seem sound but there are no observations available that can prove or disprove them.  She used the term borrowed from a colleague – ascientific to describe that phenomenon.  I think it is a much more accurate term than unscientific. 

3:  A detailed text on the information exchange between psychiatrists and patients. We talk and teach a lot about interviewing techniques but never address the details like: Is there an absolute minimum or maximum? And how can it be determined?

4:  A detailed text on biological complexity in medicine and psychiatry. Our literature is full of references to heterogeneity and suggestions about how to deal with it.  There is very little commentary about how this originates in the biological complexity of living organisms.  We study it from the basic science side but there is no consolidation with what we observe clinically.  At that point it becomes more of a political argument with suggestions that it needs to be controlled in some way or that there are better measures for it.

5:  A definitive text on clinical trials in psychiatry.  If you pick up texts on clinical trials in medicine you will rarely see a reference to psychiatry. I can read any number of clinical trials in the field and show how deficiencies or practicalities may have affected the results.  Psychiatry probably has more meta-analysis of clinical trials than any other specialty and yet the data has more deficiencies.

6:  The only philosophy that really interests me is Van Fraassen's work on empirically adequate models and how that applies to medicine and psychiatry.  It seems fairly clear to me that this is the way we are taught in college, medical school, and residency and yet there is surprisingly little commentary about it. Instead we see elaborate philosophical theories about psychiatry that typically illustrate that the author(s) either knows very little about psychiatrists or how they are trained or they have an entirely different agenda and need to attack the field to advance it.  

7:  Clinical trials with small effects do not interest me.  The same is true for meta-analyses of those trials and pilot studies.  I am much more interested in innovative analyses of that data or innovative designs.  I am interested in the gamut of diagnostic and therapeutic modalities as well as preclinical and basic science studies.  We are in need of better clinical trials technology and have been for at least 20 years. 

These are just a few of the priorities that I think about daily.  And I would happily read those texts or book chapters and review them.  In fact, if anyone at the American Psychiatric Press or Mayo Clinic reads this blog, I am looking forward to Keith Rasmussen’s Ketamine – The Story of Modern Psychiatry’s Most Fascinating Molecule especially the chapter Recreational Use of Ketamine: The World Discovers the K-Hole. Send me a copy and I will read and review it.

A few considerations for anyone interested.  My writing style is too dense at times and people editing my writing often suggest fewer words.  I must admit editing helps greatly. Unfortunately, I don’t have an editor apart from what happens in the word processor.  So you might have to deal with that in the final product. My preferred format is PDF, largely because I have no space left for books.  The picture above is a random half shelf sample from my library.  I have 36 full shelves and 16 half shelves in the room where I am typing this as well as an additional storage room in my basement full of books.  I can guarantee that no one else will see any PDF sent my way and have successfully restricted access to thousands of papers and drafts sent to me over the years.   

The content of this blog is open access and reusable.  According to the CC licensing it just requires crediting and referencing me. I do not make any money on this blog and there are never any charges. Any book or chapter review done could be copied and pasted to any online site and I would be happy to post it on Amazon myself.

I am currently the co-editor of a small newsletter and do not want any additional editorial work.  I also do not seek any peer review positions for journals largely because that experience for me has not been a good one.

Consider this post a hopeful clarification. If you are thinking about sending me the final version of a book, book chapter, or paper and need additional information – feel free to email me with questions before sending anything.

 

George Dawson, MD, DFAPA

Free Associating in the MRI Scanner…

 

I finished my second MRI scan this year earlier this afternoon. So far lifetime – I have had 5 and will have 6 by the end of next month.  I am sure that many people reading this have had the experience and I would not rate it as pleasant at all.  Just the obsessive checklist that must be completed prior to the scan is enough to raise the anxiety level. Is my body free of implanted or tattooed or accidentally placed metals?  When they were scanning my pancreas – my first thought was: “What about that laparoscopic cholecystectomy I had done in 2019?”  I had read the operative report and it described two permanent clips being placed on the cystic duct prior to dividing it and removing the gallbladder.  I contacted the surgeon about that and he was certain the clips were not ferromagnetic.

One of the last questions is: “Are you claustrophobic?”  And if you are is your primary care doctor prescribing a sedative and if you take that sedative is there somebody here who can drive you home?” I would be hard pressed to think of many people who would not be claustrophobic in an MRI tube.  After all you are in a tight space with very loud noises for a prolonged period. As the radio frequency waves are generated the tube heats up.  It is better than hurtling through space in a larger tube during air travel – and I smiled to myself as I thought of the comparison.

In all cases I have been given a headset and asked about musical preferences and volume.  So far, the headsets don’t block the sound of the machine and obviously are not noise cancellation devices. It did lead me to think about designing headsets without ferromagnetic materials and what that might involve. The only designs I have seen so far use air conduction through tubes rather than electrical connections.

Music selection is as much of a problem as the low-fi headset.  I forgot to ask if I could use my own playlist – but it was safely locked up far away from the 1.5T magnet. I tried to be more specific this time: “Have you got any Canned Heat?”  My most recent play list starts with 3 Canned Heat songs from 1967 – but looking at the tech I estimated he was born in 1980 and the other in the 1990s.  When they rolled me out of the tube one had been replaced by a woman with brightly colored hair who may have been born in the 21^st century.  I changed my answer to “Classic rock.”  That can be a disappointing genre because too much of it is bubble gum music.  Over the 30 minutes in the tube, the heaviest it got was AC/DC Highway to Hell and James Gang Funk 49.  I did enjoy Steve Perry (Journey)  and was tempted to sing along like I do in the car.  But I am sure that would have not been a good idea and may have resulted in additional imaging time and I can no longer hit the high notes.

My mind wandered to fMRI research. How in the world can research subjects be expected to produce real world results from inside the catastrophic MRI world?  I decided not to include my real catastrophic thinking in this post because it is idiosyncratic and I don't want to affect anyone else's decision to get an MRI scan.  And today I just had one or two brief thoughts. I spend most of the time in the tube actively distracting myself and doing sigh breathing exercises to control my heart rate.  Today I opened my eyes in the tube – briefly for the first time.  All I could see was an expanse of whiteness in front of my face with a row of fasteners bisecting the field.  I was pleasantly surprised to find it was about 6 inches away – farther than I had imagined it.  

While I was thinking about research, I also thought about all of the MRI scans I had ordered on my patients.  Going through the procedure yourself leads to questions about the how it is presented to patients for informed consent. I was careful to describe the issues with confined space and noise as well as the advantage of no radiation and better resolution.  Being hospital based, I had the advantage of an anesthesia team being available to sedate and monitor patients who were unable to tolerate it. As I was showing one person their results by holding the film against a window in their room they fainted and I was able to catch them on the way down.  The realistic appearance of the brain in that scan led to that reaction.

Forty years ago, I was an intern in this hospital. My very first rotation was Internal Medicine.  Back in those days it was a county hospital.  Today it is a massive flagship hospital of one of the largest health care organizations in Minnesota. That included a building program to the tune of hundreds of millions of dollars. The original hospital remains at the center, but it is obscured by new wings and buildings. The parking lot I parked in did not exist at the time.  There was a lot out front that you accessed with a magnetic card.  One night I was working late and a guy approached me for money as I entered that lot. I handed him $20 to avoid what I thought might be coming. It was a tough neighborhood.

Once you enter the building – you can step back in time where old meets new.  One of those places is medical imaging. During internship and in the 22 years I worked there radiology (as we used to call it) was one of my favorite haunts. I knew the radiologists and knew I could ask them questions about films.  Surprisingly many of them had questions about psychiatry. Before the electronic health record, I would make a drawing of the positive findings from CT and MRI scans and redraw it in the patient’s chart.  As radiology became digitized it was easier to cut and past images.  I could still discuss images with the neuroradiologist.  I missed all of that when I left that practice.

The MRI tech comes over the headphones:  “OK we are going to come in and inject the contrast.”  They know I had a mild reaction to CT scan contrast but the MRI contrast is gadolinium based and I have had it before.  The last time they checked my pre and post creatinine levels, but at this facility that is replaced by questions about renal insufficiency and dialysis.  That seems like a low bar.  He checks in again in 5 minutes to make sure that I am not having a reaction.

Another sequence of radiofrequency waves starts and there is a pulsating beat that reminds me of a rock and roll song.  I try to recall the song just based on the beat.  I check my muscle tension and realize my shoulders are rolled forward – so I force myself to relax, move my neck, and do some patterned breathing. I would really like to hear some Nirvana at this point.

The tech is on the headphones again.  “OK you are doing great – 5 minutes left.”  That reminded me of a previous scan when I got a similar message and remembered all of the songs that played afterwards.  This time ZZ Top LaGrange comes on. It is a 4 minute song.  At the end – they roll me out of the tube and tell me I have done a great job.

Last night I was wondering whether I was getting progressively more anxious about MRI scans or whether this was a form of exposure therapy. I was surprisingly calm during this one and more confident that I will live to MRI another day.

 

George Dawson, MD, DFAPA

Supplementary:  I have received some early feedback on why I am getting these MRI scans. First and foremost - I am interested in addressing serious problems and preventing disability. I personally know many people who were disabled as the result of spinal injuries that occurred from seemingly trivial events like turning to see someone walking through the door or turning over in bed. I am also aware of age related injuries that occur in active people. Falling off your bike at age 70 is not the same as falling off your bike at age 30 or 40.  All of these scenarios suggest to me that numerous age-related changes in the spine in the absence of any course of effective strengthening can lead to catastrophic problems.   

In addition to the symptoms, I would like to get an opinion of whether it is safe to do aspects of my exercise routine.  I would really like to get back out on the ice speedskating - but I am not going to if it means I will get progressively disabled from spinal problems.  I saw Lindsey Vonn speak to this recently.  I am certainly not comparing myself directly to one of the greatest skiers of all time - but I could relate to why she finally decided to quit.  

“My body is broken beyond repair and it isn’t letting me have the final season I dreamed of,” Vonn said. “My body is screaming at me to STOP and it’s time for me to listen.”   

A lot of aging athletes like myself have the thought that as long as we exercise and stay very active - we will be able to continue in sports as long as we want.  In retrospect, I think I have shown that you can certainly push it much farther than expected and much farther than average - but like the best there is a breaking point. 

Without yet knowing the result of this scan - the possibilities are significant. In the ideal world, it will show age related changes and that would just indicate continuing the physical therapy that I have been doing for 20 years.  If a potential surgical problem shows up that is more complicated.  I do know skaters who have had back surgery and most back surgery has highly variable results. I have also observed and assisted on many back surgeries in medical school where neurosurgery was my preferred surgical rotation - but I assume surgical technique has improved greatly since then.  Would I get back surgery if there was a high likelihood of symptomatic relief and I could return to skating?  Would I get back surgery without that guarantee?  All of that is up in the air at this point. 

Image Credit:  Image credit and Creative Commons licensing can be obtained by clicking directly on the image at the top of this post.

Are Medication Trials For Depression Too Long In Duration?

Depression is a significant cause of disability in the world.  That is complicated by the fact that there are not enough resources to treat people with depression, access is rationed in many areas including the United States, there is a high rate of attrition during treatment, and depression is often associated with significant medical and neurological disability further restricting access to adequate care. 

Over the past 30 years, strategies for treating depression have increased considerably since antidepressants medications are not uniformly effective and they have side effects that may not be well tolerated.  Antidepressants have evolved over the years from monoamine oxidase inhibitors to tricyclic antidepressants to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and norepinephrine dopamine reuptake inhibitors (NDRI).  The suggested pharmacology of more modern antidepressants is even more complex and the initial classifications may mean a lot less than what was initially hypothesized.

Although antidepressant monotherapy is the preferred treatment path – failure of one or two rounds of antidepressants can result in combinations of augmenting agents designed to improve treatment response.  Early augmenting agents included triiodothyronine, thyroxine, and lithium.  More recent augmenting therapies include additional antidepressants (typically bupropion), aripiprazole or brexpiprazole, or buspirone.  There are several additional agents that are used in lower frequencies.  Context is important in considering the origins of the augmenting therapies. When thyroid hormones were added, there was an active research focus on neuroendocrinology including the impact of physical illnesses on thyroid function. Later focus on treatment resistant depression assumed that all depression was treatable - it was just a question of finding the correct treatment. Both hypotheses have had low yields. 

The relative advantage of these approaches is that they are potentially cost effective (most antidepressant medications are generic and prescribed by non-psychiatrists), they are readily available, and they are more culturally accepted than they used to be.  The disadvantages include side effects most commonly nausea, vomiting, diarrhea, sexual side effects, and dry mouth. Patients need close monitoring initially to prevent side effects and assure that the medication is working. The physicians doing that monitoring also have to be aware of rare serious side effects that require emergency treatment – like serotonin syndrome, neuroleptic malignant syndrome, and acute neurological side effects.  A good knowledge of general medicine is also required to avoid treating people with chronic illnesses where there are contraindications. 

Another disadvantage is treatment non-response.  What happens if two different prescriptions are tried for adequate amounts of time and there is no response. Where does the treating physician go from there?  Seeing thousands of patients well into a course of treatment for depression and/or anxiety this is a very common problem – often complicated by additional problems including insomnia and substance use disorder.

Before anyone suggests addition exercise or psychotherapy at that point – practically all patients seeing psychiatrists have already done that.  Most of the people I treated had seen more than one therapist and these days they are branded therapists (CBT, DBT, IPT, etc).  The only non-pharmacological modality that was rarely used was bright light therapy and I typically discussed that as an add on to antidepressants. That therapy requires purchasing a device and using it for set periods of time each day. 

For the people with severe treatment resistant depression, more complicated interventions including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and ketamine (intranasal, IV, IM) are on the horizon but difficult to find in one place.  As an acute care psychiatrist, I had very easy access to ECT.  As an outpatient psychiatrist there was essentially no access, even when I called the facility where I previously worked. Because of the current systems problems, my patients needing ECT had better access if they presented to emergency departments where they knew ECT was an option and got admitted to that hospital. The same barriers seemed to preclude any contact with me as an outpatient psychiatrist.  No calls for a collegial discussion and in many cases no discharge records from the treating facility.  Siloed care these days is a major impediment to care.

Last weekend, I was exposed to a modern approach that concentrated all the advanced treatment modalities in the same clinic that happened to be staffed by researchers interested in treatment resistant depression. Before I get to their approach – I designed the slide at the top of this post to illustrate the standard approach to moderate to severe depression over the course of my career starting in 1984.  I remind readers that psychiatrists are seeing a highly selected group of patients who have probably already failed several antidepressants and psychotherapies.  As time goes by and the number of non-psychiatric prescribers continues to increase greatly – that selection process will greatly intensify.

Looking at the general scheme of antidepressant approaches to only depressive disorders (DSM major depression and persistent depressive disorder) – there has been a clear progression of newer medications designated by older class names like tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). These general class names have significant limitations – not the least of which being reuptake blockade by of specific transporters is probably only part of the mechanism of action and some class designations depend more on chemical structure than physiology. If anyone would like a second explanatory slide with all of the current FDA approved antidepressants and more modern nomenclatures – let me know and I will make the slide.

In treating significant depressions – psychiatry added adequate dosing and duration and therapeutic drug monitoring (TDM) to determine adequate trials of antidepressants therapy.  There were active debates and research suggesting 6 weeks might be adequate on the lower end and 16 weeks as adequate duration on the high end. Pharmacokinetic factors came into play with some antidepressants with longer or shorter half-lives. If an adequate trial of medication was completed there was the question of “What’s next?”  The next issue was either changing the antidepressant or adding an augmenting therapy (adjunctive therapy per the FDA).   As noted in the graphic thyroid hormones (Triiodothyronine or T3 and tetraiodothyronine or T4/thyroxine) were both used early on in doses that were typically much lower than physiological doses (25 – 50 mcg) as well as stimulant medications (amphetamines). As time went by additional adjunctive strategies were added.  The first study of adding lithium to tricyclic antidepressants occurred in 1981 (1).  Adjunctive medications started to take off in the early part of the century with pharmaceutical companies getting that indication for newer antipsychotic medications that also had bipolar disorder indications (see specific dates of approval).   

The upside to these strategies was that antidepressant effects could be improved often to the point that depression remitted. The potential downsides were twofold – the burden of taking a second medication that could introduce new side effects or synergistic side effects with the current therapy and the prospect of endless medication trials.  Now there was the additional time of seeing whether any of several adjunctive therapies worked in addition to the antidepressant monotherapy trials. Although I did not indicate it on the diagram – several antidepressant combinations were also suggested and some patients were taking 3 or 4 antidepressants at once.  That was a significant departure from quality metrics used in the late 20^th century where antidepressant monotherapy was the rule.

The concept of treatment resistant depression – generally defined as a failure of a specified course of pharmacotherapy was often stimulus for these trials. The application in clinical practice was not as clearcut because of the number of choices and how individual patient factors affected those choices. Acuity, disability, and access were the usual limiting factors leading to cessation of pharmacotherapy trials and a trial of neurostimulation like electroconvulsive therapy (ECT).

Last week, I saw a unique solution to this bottleneck problem presented by C. Sophia Albott, MD, MA entitled  “Next Generation Treatments for Resistant Depression: The UMN Interventional Psychiatry Approach.”  She described a well-staffed clinic with a stimulating practice environment that offered ECT, transcranial magnetic stimulation (TMS), ketamine (intranasal, IM, and IV), Vagal Nerve Stimulation (VNS), and Behavioral Activation Therapy provided to all the patients in their clinic.  Their general hierarchy was to start with TMS and if that was not effective to branch out into other specific therapies. The overall description of the clinic and some of their early successes suggests to me that this is potentially a good approach.  The idea of these therapies all being concentrated in one place, taking over treatment of the patient until they are in remission, and additional support is what is lacking in most systems of care.

I am sure that some would wax philosophical about similar clinics being the future of the field – but there still needs to be psychiatrists out in the community providing acute care and consultation to primary care physicians. A subspeciality clinic could function well as back-up those psychiatrists who often lack a referral resource for neuromodulation and other advanced techniques.  The largest potential benefit would be to patients who are being maintained in long term medication trials longer than they should be. This approach may be the best way to shorten the period of disability and suffering from difficult to treat depression as well as the adverse effects of polypharmacy.

George Dawson, MD, DFAPA

 

References:

1:  Dé Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry. 1981 Mar;138:252-6. doi: 10.1192/bjp.138.3.252. PMID: 7272619.

2:  Trivedi MH, Rush AJ, Crismon ML, et al. Clinical Results for Patients With Major Depressive Disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry. 2004;61(7):669–680. doi:10.1001/archpsyc.61.7.669

3:  Sonmez AI, Wilson S, Olsen S, Sullivan C, Herman A, Widge A, Nahas Z, Albott CS. Outcomes from University of Minnesota Clinical rTMS Clinic for resistant depression: naturalistic data on suicidal ideation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 2021 Nov 1;14(6):1652.

4:  Papakostas, G.I., Trivedi, M.H., Shelton, R.C. et al. Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02468-x

Two Million Reads - A Blogging Milestone of Sorts

 

Last night around midnight – I noticed that I had crossed the 2 million reads mark on this blog.  The Google Blogger interface that I use is not very granular so it is difficult to tell how many of those hits are actual reads as opposed to something else. By something else I mean hackers, bots, and people trying to use my blog for free advertising.  The products are typically illegal or barely legal drugs or psychiatric services outside of the US.  The increase in VPNs is also probably a factor.  Over the years the number of hits per page has flattened out while the overall number for the blog has increased. My assumption is that individual page reads with a VPN are not counted, but they are counted for the overall blog.

I am reassured and very grateful for the readers of this blog and have corresponded in detail with many of them.   They range from medical students considering a career in psychiatry to very senior medical scientists with hundreds of research publications.  In many cases they are advocating for a specific viewpoint.  In a few they want me to change a blog post in some way.  That rarely happens because of my level of experience and the degree of research I put into these posts.  Somewhere in the past I pointed out that one of my motivations for writing this blog came from colleagues who asked me what I read, where I found certain information, and how I came to know what I know. I hope I am successful at getting that information out there.

I am also very grateful to the academics out there who share their work and give me free advice.  One of the most striking examples was midnight correspondence with two philosophers who wrote a book about diagnostic decision making in the late 1980s. I used it to teach a course in not making diagnostic errors in medicine and psychiatry. Both professors were retired and I sent them emails in a later time zone at midnight. They gave me detailed responses within an hour. I don’t always get a response, but when I do it is exhilarating to be a part of academic discussions with some of the most accomplished people in the world.

It has not always been a walk in the park.  I was confused about gaslighting initially and tolerated too much of that activity before drawing a line.

I often wonder about why people read or do not read this blog.  The appearance is fairly basic compared with other sites that offer better graphics.  I think there is some reluctance or resentment based on the idea that I am profiting from this blog.  I can restate that this is completely non-commercial and not-for-profit.  I not only have not made a cent writing this blog but have had to pay licensing costs out-of-pocket for graphics and permissions.  A friend and colleague recently told me that he never thought about reading blogs.  The era seems to be one of podcasts and TikTok video clips. I have always found reading to be a lot faster.  And unlike TikTok I am intentionally not provocative.

One of the recurrent themes here on my blog is that there is no way to simplify psychiatry and do it well.  A psychiatrist considering themselves to be primarily a psychotherapist or primarily a psychopharmacologist is not considering large areas of the discipline.  The same is true of the psychiatrist who ignores medicine and neurology.  To paraphrase Euclid (325 BCE - 265 BCE)  “There is no royal road to psychiatry.”  You must know it all to do good work.  Complexity is good and necessary in human biology.

I currently have 123 folders in my References 2024 Folder and it’s only March.  I am working on a protocol that will allow me to submit research papers and blog them if they are rejected.  At the rate I am going I will write my own textbook in psychiatry in another 20 years.  Stay tuned!

 

And Thanks again!

 

George Dawson, MD, DFAPA

An Unpublished NEJM Letter

 

 I was notified this morning that a letter I sent in to the New England Journal of Medicine would not be published because they had limited space.  Anyone sending a letter is notified that if the letter does not respond to one of their articles you are limited to 400 words.  If your letter does respond to an article the word limit is 200 words.  I was responding to an essay by Lisa Rosenbaum, MD (1) and whether medicine is a calling or just a vocation and the implications that each of those categories have.   My first attempt at the 400-word mark (374 actual) is below:

 To The Editor:  The essay by Dr. Rosenbaum (1) highlights a critical issue in medical education, research, and practice.  Much of the analysis is dependent on the concept that medicine is either a job or a calling. The critical factor in all settings is the practice environment.  Over the past 30 years we have seen a severe deterioration in that environment and how it impacts physicians. 

Forty years ago – physicians were valued as knowledge workers.  Work quality was emphasized and teaching departments were run by senior physicians who emphasized teaching and research.  They were models for focused lifelong learning and were able to maintain interest and enthusiasm in their departments by balancing clinical demands and those learning tasks. Trainees in the department benefitted from identification with these physicians as well as learning clinical approaches in their specialty.  The department head often had a business administrator in the department, but there was no doubt that the focus was medicine first and business tasks were minimal.

Over the past several decades, business and political interests have changed the physician role to production workers. Physicians are now valued in corporations for productivity and all the administrative time that takes. Department heads are often more focused on business matters than teaching and research.  Meetings take on a business rather than academic orientation.  More time is spent learning about the business environment rather than learning medicine.  The administrative burden alone easily exceeds the time used in the past for teaching rounds and conferences.  This burden has also decreased physician efficiency and added hours per day producing documentation for billing purposes that is repetitive and excessive. It also detracts from the physician patient relationship that is further fragmented by physician extenders.

The modern practice environment is not conducive to producing and motivating physicians.  Rather than an environment where experts can have spirited exchanges about medical care – it is one where experts are second guessed by administrators with no medical training.  It is an environment that does not produce a calling.

Recognition of the severe deterioration in the practice environment is the first step in correcting the problem.  Steps need to be taken to restore practice environments to stimulating settings that can lead to a high level of expertise, quality, and humanistic care.    

 

George Dawson, MD, DFAPA

 

References:

1.  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

 

The final 200-word final submitted version is below:

 

Rosenbaum argues doctors' declining job satisfaction stems from corporatization, generational changes, and a shift to production-style management.¹ Traditionally, senior physicians oversaw the practice, fostering a learning and research environment. Forty years later, business managers treat doctors as production workers² in an increasingly inefficient environment. This clashes with physicians’ role as knowledge workers, requiring intellectual stimulation, collegiality, and patient-centered care.

That change is responsible for a marked deterioration in the training and practice environment.  Business practices have been emphasized to the point that there has been an adverse effect on physician time management for professional and personal activities. It is also a direct cause of burnout.³

Physicians function best as knowledge workers consistent with their training. Physicians have been forced into the role of production workers. The solution is not to develop a rhetorical response to being in that role. The solution is not an idealization of the “good old days” – but recreating and restoring the physician knowledge worker environment.  That is the first step toward making physician sacrifice meaningful again.

 

George Dawson, M.D.

 

1.  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

2.  Drucker PF. Knowledge worker productivity – the biggest challenge.  California Management Review 1999; 41: 71-94.

3.  Lacy BE, Chan JL. Physician burnout: the hidden health care crisis. Clinical gastroenterology and Hepatology. 2018;16(3):311-7.

 

It took me 5 rewrites to get to progressively less words.  When you tend to use as many words as I do that was a painful process.  If you are a blogger the pain is compounded by the fact that editorial control is lost and you cannot publish your comments anywhere else (including a blog) if you hope to get them published in a journal.  The NEJM has a 3-week deadline for letters based on their articles.  It took them 5 weeks to reject it. They obviously can publish whatever they want and provide whatever rationale that they want – but the space argument seems thin.

Let me suggest why I thought this letter – even pared down to 170 words was important enough for me to send.   A brief review of Dr. Rosenbaum’s essay is necessary and if you have access, I encourage you to read it.  The essay begins with standard blue-collar rhetoric rooted in reality – basically that the working man is subjected to the whims of corporations who rarely have their interests in mind.  A young physician from that family concludes that the idea of medicine as a calling is using that term “weaponized against trainees as a means of subjugation— a way to force them to accept poor working conditions.” 

The problem with that analysis is twofold.  First, trainees do not have a monopoly on subjugation by corporations or the government.  It has been a decades long process directed at practicing physicians.  Second, rhetorical “weaponization” of terms applied to the profession is unnecessary.  That battle has already been lost. The current work and training environment has been deliberately shaped by the managed care business and like-minded governments for the past 30 years. Businesses don’t have to use weaponized rhetoric.  All they have to do is replace physicians with non-physicians, tell them they can work somewhere else, or reduce their compensation or just not pay them if they don’t meet their productivity expectations. They can also use internal committees and business practices to scapegoat and gaslight physicians who they do not like.  There is essentially unlimited leverage to get what they want.  All those measures are far more powerful in getting physician compliance than suggesting they need to make sacrifices in the service of a calling.  Physicians today are expected to make significant sacrifices or else – all in the service of their business masters.  It is evident the young physician in the essay knows nothings about it. The only practice and training environment that he knows is the one that has been severely compromised.

From medicine-as-a-calling, Rosenbaum introduces us to workism.  This term was coined in an Atlantic magazine essay to suggest that somehow work is a central part of life, identity, and meaningfulness is life.  That author goes on to suggest that people born between 1981 and 1996 were encouraged in this attitude and found themselves instead in debt and with no meaningful life work.  That led to demoralization and nihilism about capitalism.  When I read these paragraphs, I had to wonder how naïve this generation could be?  How could they possibly think that American capitalism and the economy was good for anybody?  Don’t they read anything about the environment, pollution, climate change, environmental catastrophes, unnecessary wars, near economic catastrophes – all precipitated by American capitalism?  I don’t think the idealization of work or capitalism explains the lack of medicine-as-a-calling.

There is a glimpse of reality in the next section when we hear how of how a long-time residency director of internal medicine stepped down due to a misalignment of the missions of hospitals and training programs. That is really putting it mildly. In many cases that difference was all it took to destroy training programs.  It is common to hear how residents are just used as inexpensive labor – but that has always been the case. The real problem is that the quality of teaching is adversely affected when faculty are told that they must max out their productivity and at the same time – get no credit at all for teaching.  

Rosenbaum’s essay depends on generational stereotypes and barely touches the root of the problem.  I reference the work of Peter Drucker – widely considered a guru in business management.  He pointed out the differences between production workers and knowledge workers. Basically, knowledge workers are quality focused in areas that they have more expertise than the management does. They are generally felt to be critical to the business and the idea is to retain them and give them adequate resources. Establishing a culture of excellence in their knowledge base adds to the environment. Production workers are engaged in repetitive tasks.  Their supervisors generally have worked their way up from doing the same tasks and therefore know as much about their work.  Early experiments in mass production showed that analysis of the repetitive tasks by so-called efficiency experts could improve the overall production.

What has occurred in the past 30 years has been the mass conversion of physicians from knowledge workers to production workers. The associated practice and academic environments have suffered drastic changes. Academic physicians have found that a major part of their work – teaching and research has been devalued in many cases to nothing.  In the meantime, they are expected to see many more patients, often to the point that they find themselves in new clinics – just to increase the overall billing.  The electronic health record (EHR), billing, and coding, and maintenance of certification are all added time penalties with no associated productivity credit. They have little say about how they see patients or how many patients they see.

I will cite one of many examples to highlight these points.  Just 5 years ago,  an internist I know was audited by his managers who had him tracked from 8AM to 4PM by an efficiency expert. That time frame encompassed 90% of his patient contacts, but only 66% of his workload.  Every day when the efficiency expert left – he would ask: “Where are you going? I am here for another 4 hours.”  The managers wanted to use the efficiency expert report to suggest that he was not efficient enough in seeing patients – but the real problem was the lack of clerical support and the EHR. The exercise was enough for the internist to realize he was working in a hostile environment and he moved on.  A clear loss of a knowledge worker.  The corporate myth that everyone is replaceable missed again in this case. This internist had experience and skills that could not be duplicated by anyone else in that clinic. This cycle of corporate flexing repeats itself thousands of times per day.

There can be no calling to work in such an environment where your work is routinely denigrated and devalued.  It plays out as a personal attack. You will necessarily feel like a production worker and start to work on the goals of production workers like standardized working conditions, hours, and benefits.  When you come home at night – you will leave the job behind you and no longer think about the patients who have problems with no solutions or what you need to know to do a better job. There is no esprit de corps of cohesion, support, and invigoration necessary for a stimulating knowledge worker environment.

That is the recent attitude and it correlates directly with the business takeover of medicine – not the newest generations.  It also correlates with prominent editorials in the top journals of our field like the New England Journal of Medicine.  These editorials illustrate on almost a weekly basis that there is no end to the businessmen, politicians, and lawyers who want to run and ruin our profession.  To date – they have been tremendously successful.  There is also no lack of evidence that the medical profession has been completely inadequate advocating for a reasonable practice and training environment.

Medicine will never be a calling again until the work and practice environment has been repaired and removed from the complete control of businesses and governments.

And yes – it is that simple.

George Dawson, MD, DFAPA

 

References:

1:  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

2:  Drucker PF. Knowledge worker productivity – the biggest challenge.  California Management Review 1999; 41: 71-94.

Graphic Credit:

All details at this link.  Coming from 4 generations of railroad workers it was a natural choice:  

https://commons.wikimedia.org/wiki/File:Group_of_laborers_digging_through_dirt_pile_along_railway_bed_LCCN2016647134.jpg

Kendler Keeping It Real…..

 

Kenneth Kendler, MD needs no introduction to anyone even vaguely familiar with the psychiatric literature.  If you need to do your own research his accomplishments and scientific papers are widely available on the Internet. This post is to focus on his recent commentary in JAMA psychiatry (1) over the issue of psychiatric diseases and whether or not they are brain diseases.  He starts out with a 1867 quote from Griesinger stating that the brain is the only logical origin for symptoms of insanity. His analysis is at the level of “pathological and physiological” factors.

He briefly reviews two common arguments about whether psychiatric disorders are brain diseases.  The first Cartesian dualism that a mind emerges from the brain and is not the same as a brain. Since a brain is necessary for all mental phenomenon there is no specific answer to the question about whether the phenomenon observed with psychiatric disorders are diseases.  The second common argument is that grossly detectable brain diseases (lesions at autopsy and sophisticated imaging)  eventually became the purview of neurology.  To complement Kendler’s commentary, I would add that this has never been strictly true since both overt lesions and physiological brain dysfunction has always been studied by psychiatrists.  It has been a common antipsychiatry argument advanced by Szasz and others based on 19^th century concepts.  Ron Pies (2) has recently commented that it involved a misunderstanding of Virchow’s work on pathophysiology.   

An indirect way this problem has been handled is to suggest that it has to do with the vague definitions of disease (3).  Without a clear definition, anyone can use their own to declare that psychiatric disorders are not diseases. That has been a common tactic used to declare that not only that mental illnesses are not diseases – because of the lack of clear gross pathology they do not exist.  Dealing with the problem at this rhetorical level has not been very successful largely due to the lack of interest in rhetoric on the part of medical professionals and constant repetition by the rhetoricians.

More practical philosophical attempts at disease definition like loss of function models seem to not have much traction. Munson and Resnick (4) proposed one of these models and also suggested that the loss of function is related to programming errors in biological processes.    

Kendler suggests a clear path that has appeal to anyone who has studied pathophysiology and treated illnesses without clear lesions or with lesions that had to be the end product of some unknown pathophysiology.  That group of people would be anyone who has done an internship or residency in any medical field.  Anyone with that experience has seen a wide array of medical conditions that are polygenic in nature and have either an unknown or highly speculative pathophysiology.

The suggested path is genetics-> pathophysiology or more broadly “genetics -> brain -> schizophrenia.”  Rather than bemoaning all of the failed GWAS studies and Decade of the Brain, Kendler cites “the most robust empirical findings in all of psychiatry—that genetic risk factors impact causally and substantially on liability to all major psychiatric disorders.”  More specifically he cites a 2022 report that shows that gene expression (as mRNA levels) of risk variants for schizophrenia were noted in the brain and no other tissue.  That brings the brain expression in his causal link into clear focus. 

At that point he hedges and suggests that this may not be robust enough to suggest that a brain disease is occurring. For me it is plenty.  He goes on to suggest that there are 5 advantages of this approach including data driven rather than metaphysical, bypasses the 19^th century need for gross lesions, fits with pluralism or multiple possible etiologies, can potentially provide information about other diseases affecting the brain, and avoids a hard line of demarcation between normal and disease at the physiological level.  The last point has been elaborated in the more recent past as quantitative versus qualitative diseases and the associated variants. 

On the limitation side – a genetics only approach is the main consideration.  The antipsychiatrists that he has alluded to may be realizing that they need to finally modify their 19^th century rhetoric and I have seen the equally absurd claims that there are no genetic effects for psychiatric disorders.  The difference is that Kendler is an expert in the area – so only the most dedicated post modernists will claim that they did their own research and came to a different conclusion.  He does see the innovation of being able to detect tissue levels effects of genetic variants as a good starting point.  The goal is to elaborate the functional networks affected by these variants, describe mechanisms at the molecular level, and how those mechanisms are affected by variants (5).

This is really an inspiring commentary at a time when it is getting more fashionable to attack basic science research in psychiatry. I saw a comment just last week about how biological psychiatry was a drain on mental health research.  And there are frequent comments about how there should be more psychosocial research, even though there is no clear evidence that is necessary.

As a clinical psychiatrist and a physician first, my observations have been that most people go to medical school to gain knowledge about the human body and how to treat, prevent and where possible cure diseases. Speculative pathophysiology and mechanisms are all part of that starting in the first two years of basic science course and extending to clinical rounds at bedside during residency.  Philosophy and endless arguments about the nature of disease or psyche is not.  Psychiatry has lost its way many times due to an inability to recognize and respond to rhetoric. Kendler’s solution to the question of whether mental disorders are brain diseases is an elegant one and it is consistent with the way physicians are trained.  It also establishes a boundary that some questions in psychiatry are not answerable by philosophy.

Finally, what is still lacking?  I think that ultimately, we want medicine and psychiatry to be part of a comprehensive view of human biology. We need more comprehensive theories about human biology and how things really work at the physiological and molecular level.  That knowledge is currently spotty across all specialties. Biology theory rather than biological psychiatry is really the goal here and we can use more input from theoretical biologists of all specialties.

George Dawson, MD, DFAPA

References:

1:  Kendler KS. Are Psychiatric Disorders Brain Diseases?-A New Look at an Old Question. JAMA Psychiatry. 2024 Feb 28. doi: 10.1001/jamapsychiatry.2024.0036. Epub ahead of print.

2:  Pies R.  Did Szasz Misunderstand Virchow’s Concept of disease? Psychiatric Times. Feb 21, 2024.  https://www.psychiatrictimes.com/view/did-szasz-misunderstand-virchow-s-concept-of-disease

3:  Pies RW, Dawson G.  Epistemic Humility in Psychiatry: Why We Need More Montaigne and Less Savonarola.  Psychiatric Times.  Oct 19, 2023.  https://www.psychiatrictimes.com/view/epistemic-humility-in-psychiatry

4:  Albert DA, Munson R, Resnik MD.  Reasoning in Medicine: An Introduction to Clinical Inference.  Baltimore, Maryland: The Johns Hopkins University Press, 1988: 150-180.

5:  van Dongen J, Slagboom PE, Draisma HH, Martin NG, Boomsma DI. The continuing value of twin studies in the omics era. Nat Rev Genet. 2012 Sep;13(9):640-53. https://doi:10.1038/nrg3243

.