Recent Opinion About Diagnostic Heterogeneity – Gets It Wrong

There was an opinion piece about categorical diagnosis in psychiatry and diagnostic heterogeneity that was published in Psychiatric Research weeks ago (1), that generated a lot of controversy.  The controversy started when an online publication characterized the article as showing that Psychiatric Diagnoses Found to Be "Scientifically Meaningless".  The author of that article subsequently posted that the article was written by science undergraduates re-purposed as science writers.  If this was supposed to be investigative journalism it failed at several levels not the least of which is the apparent conflict of interest by the authors. Instead the internet article basically quotes the authors as factual and scientific rather than a rhetorical opinion piece.  What follows is my take on the Psychiatric Research Article.

The first sign of bias that a reader may encounter in the original article is right in the abstract. The concluding sentence reads:

“A pragmatic approach to psychiatric assessment, allowing for recognition of individual experience, may therefore be a more effective way of understanding distress than maintaining commitment to a disingenuous categorical system.” (my emphasis added).

When I read this sentence, it was difficult for me to believe that peer reviewers for a psychiatric journal could allow it to pass. In one sentence the authors are allowed to distort and discredit psychiatric clinical methods and diagnostic methods that have been carefully developed for over a century.  I won’t belabor the definition of “disingenuous” but it is safe to say that the expenditures in terms of brainpower and money as well as the transparency of the process make the production of the DSM 5 one of the more rigorous approaches to a diagnostic system in medicine. The people sitting on the DSM 5 committees for each section were acknowledged experts in their fields with decades of experience and published research.  Production of the DSM-5 was also a multiyear process that took 14 years to develop prior to its publication in 2015 (2).  During that time there was a multiyear grant that sponsored 13 international conferences on specific diagnostic issues.  Guiding principles and conceptual issues were examined.  Public input was solicited. Hundreds of clinicians and researchers were involved.  There was transparency about potential conflicts of interest. It was not just an intense effort – it was a unique diagnostic effort in terms of overall vigor and resource utilization.   Describing the output of all of this work as “disingenuous” and getting that in print lead me to question the peer review and editorial process.  Are the editors and reviewers ignorant of the effort that went into the diagnostic categories or don’t they care? It is clear that the authors of this article don’t.

The second red flag in the paper to anyone familiar with typical antipsychiatry arguments is the mention of Foucault and the suggestion that psychiatric classification occurs within wider sociocultural developments and that these roots have resulted in diagnostic heterogeneity.  In fact, Foucault’s observations of psychiatry were inaccurate at the time and have not held up at all over the course of time. The authors seem to ignore the actual reasons for categorical diagnosis in the first place and list none of those references.  Practically all modern DSM work can be traced back to the reference generally referred to as the Feighner criteria (3).  Reading those papers, clearly describes categorical diagnosis as a work in progress and the importance of diagnosis. The authors also describe five phases for the validation of psychiatric diagnoses.  They have this comment on diagnostic heterogeneity:

“In the absence of known etiology or pathogenesis, which is true of the more common psychiatric disorders, marked differences in outcome, such as between complete recovery and chronic illness, suggests that the group is not homogeneous. This latter point is not as compelling in suggesting diagnostic heterogeneity as is the finding of a change in diagnosis. The same illness may have variable prognosis, but until we know more about the fundamental nature of common psychiatric illnesses, marked differences in outcome should be regarded as a challenge to the validity of the original diagnosis.” p 57.

These authors suggested 5 phases to establish the diagnostic validity of psychiatric illness including the clinical description, laboratory studies, delimitation from other disorders, follow-up studies, and family studies.  There are entire texts dedicated to some of these markers on epidemiology and family studies.  One of the mandates of the DSM-5 committees was to review all of this data and compile it into the most clinically useful form.  In the interim they happened to pare the total number of diagnoses from a maximum of 297 in DSM-IV to 157 in DSM-5 (see reference 2, p xxiii).  This is the basis of categorical diagnosis – not the narrative of a philosopher.

Contrary to the idea that the current authors and the like-minded authors they have referenced have discovered diagnostic heterogeneity it has been widely acknowledged from the outset and by all current psychiatrists. There are no surprises here especially for people trained as physicians. Practically every complex biological illness is heterogeneous with heterogeneous outcomes as well as polygenic etiologies.  Their Foucauldian criticism also ignores the fact that the Washington University group was based on empirical research as opposed to the psychoanalytic process of the day.
 

The example of the empirical approach is illustrated by tracing the development of Major Depression criteria from 1950 to 1980. In fact, many in that group were highly skeptical of psychoanalysis as a possible diagnostic process at all. As they started to publish research article, one of their original articles was highly edited by a psychoanalyst/editor to remove any reference to the term diagnosis. 

The second acknowledged aspect of psychiatric diagnosis and treatment that is given short shrift by the authors is the issue the value of both diagnosis and formulation or as Kendler, et al discuss:

“However, neither we nor, we think, the developers of the criteria would claim that assessing operationalized diagnostic criteria is all there is to a good psychiatric evaluation. While critical, a diagnosis does not reflect everything we want to know about a patient. Our diagnostic criteria, however detailed, never contain all the important features of psychiatric illness that we should care about.” (see reference 4 p. 141.)

The authors’ research method is an exercise in subjectivity.  They basically read five chapters in the DSM 5 (schizophrenia spectrum and other psychotic disorders, anxiety disorders, bipolar and related disorders, trauma and stressor related disorders, and anxiety disorders) and use a technique called “thematic analysis” “to code themes or patterns of meaning across diagnostic categories being analyzed, with a particular focus on the heterogeneity or differences across types of diagnostic criteria.”  You don’t need an advanced research seminar to figure out what is wrong with that picture. Here is a group of psychologists several of whom make a career out of criticizing psychiatry and who are building a case that psychiatric diagnoses are inferior to their own vague diagnostic system using a qualitative technique that even their reference (5) refers to as having “no particular kudos as an analytic method – this, we argue, stems from the very fact that it is poorly demarcated and claimed, yet widely used”.  What outcome would any objective observer expect?

The combinatorics argument:

The authors make it seem like large combinations of diagnostic features mean categorical diagnoses are problematic.  Although they don’t say it explicitly - referring to more diagnoses greater than the number of stars in the solar system - suggests improbability.  But do large combinations of number preclude reasonable human use?  A chess board for example has an 8 x 8 square configuration and by some estimates - 10¹³⁷ moves are possible.  And yet players at all levels seem to be able to negotiate a chess board and determine win, lose or draw.  Master players can develop strategies that make them more likely to win.  Is there similar evidence that diagnoses with large combinations can be managed the same way?  What follows is a mixed table of a psychiatric diagnosis (PTSD) that yields a large number of combinations of diagnostic criteria on the left, a dimensional scale for depression (DEP) from a standard psychological test (MMPI), two different criteria for systemic lupus erythematosus (SLE), and criteria for asthma. Qualifiers for each column are listed at the bottom.

Disorder	PTSD (1)	MMPI-DEP (2)	SLE (ACR) (3)	SLE (SLICC) (4)	Asthma (5)
Criteria	Presence of 1 (or more) of the following symptoms: 1. 2. 3. 4. 5. One or both of the following symptoms: 1. 2. Two (or more) of the following: 1. 2. 3. 4. 5. 6. 7. Two (or more) of the following: 1. 2. 3. 4. 5. 6.	15/26 items	4 of 11 criteria: 1. 2. 3. 4. 5. 6. 7.   A or B 8.   A or B 9.   A or B 10. A or B or C or D 11. A or B or C or D or E	4 of 17 criteria including at least 1 clinical criterion and 1 immunologic criterion; or biopsy proven lupus nephritis: 1.   A or B 2.   A or B 3.   4.   A or B 5.   A or B 6.   A or B 7.   A or B 8.   A or B 9.   10. A or B 11. 12. 13. 14. 15. 16. A or B 17.	1. A or B or C or D 2. A1 or A2 or A3  or B or C
Minimal Combinations	3,150	7.726160e6	330	2,380	36
Total Possible Combinations	636,120	7.726160e6 + 5.311735e6 + 3.124550e6 + 1.562275e6 + 657800 + 230230 + 65780 + 14950 + 2600 + 325	12,555	321,489	46

Footnotes:

1.  This column is from the reference: Galatzer-Levy, I.R., Bryant, R.A., 2013. 636,120 Ways to have posttraumatic stress disorder. Perspect. Psychol. Sci. 8, 651–662.

2.  I have several opinions from different psychologists on the current use of this MMPI scale and the raw cut-off scores. I understand that there are different raw scores for men and women. I can recalculate this scale based on any numbers that may be deemed more reliable. Just email them to me along with the evidence.

3.  American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus

4.  Systemic Lupus International Collaborating Clinics (SLICC) proposed revised classification criteria for Systemic Lupus Erythematosus

5.  There are numerous endophenotyping classifications for asthma.  It is clear at this point there is no comprehensive system of clinical classification.

What can be observed from this table?   

Apart from waxing poetically they seem to not recognize that common psychological approaches scale to an even larger extent – much greater than 10¹⁸. I have also demonstrated that the way diagnostic criteria are worded makes a big difference in counting word combinations.  Just using the DSM phrasing “or more” greatly increases the number of combinations.  Criteria designed like the SLE criteria as a series of “A or B” choices that greatly reduce the number of possible combinations.  On the other hand dimensional criteria like a single scale from a popular psychological test – greatly increases the number of possible combinations because that scale is a many n and many k.  Using a 15/26 item scale results in 10⁷ combinations.  Using that as a ball park estimate for the other clinical scales results in numbers far larger than used by the authors to criticize categorical diagnosis.  The other aspect of this table is that less combinations is not necessarily better. With asthma for example, these numbers are based on very basic diagnostic criteria.  There are at least 2 other 6 item endophenotype systems and an additional cough variant asthma, but currently experts in the field have not developed a way to incorporate that level of clinical complexity into diagnostic criteria that would be useful to clinicians. Low number of combinations of diagnoses criteria are not necessarily better than higher numbers – especially when the disease complexity is not captured.  

The second issue with combinatorics is that they are not predictive of anything. Great strides in treating post-traumatic stress disorder have occurred in the past 30 years using criteria with a high number of combinations.  That obviously does not preclude patient selection or monitoring in clinical trials of either psychotherapy or pharmacotherapy. It does not prevent the successful diagnosis and treatment of patients in clinical settings in many cases where severe and potentially fatal psychiatric illness exists.  As an example, delirious mania had a fatality rate of 75% in 1849 in the United States (7). That number has fallen to zero with psychiatric treatment based on categorial diagnosis and the clinical training of psychiatrists to recognize severe illness. Many of those improvements have occurred in the past 30-50 years. 

  

In the authors selection strategy, large sections of the DSM 5 that clearly disprove the author’s contentions are omitted. The elimination of Neurocognitive Disorders, Sleep-Wake Disorders, and Substance Related and Addictive Disorders for example also eliminates biological markers and autopsy validation of criteria of diagnoses.  Table 1 (p. 482 of DSM-5) contains 127 discrete categorical diagnoses across 10 categories of substances. 

But the larger misunderstanding here is that what the authors disparage as heterogeneity is an expected part of medicine. Every physician knows that no two patients with asthma, benign prostatic hypertrophy, or gout are the same. There are a collection of illness features with some overlap but no truly homogeneous categories – even in clinical trials that attempt to minimize it. Biological systems especially the brain are designed to scale in various ways including based on combinatorics of various biological elements.  The author’s use of the term quadrillion, happens to be the estimated number of synapses in the brain but that is just a starting point of how systems in the human brain can scale.  The endothelial system in the human body has more cells than the brain and massive heterogeneity that allows for regulation of the vascular beds the human body. The hematopoietic and immune systems have similar levels of scaling that could also result in very large number of combinations. In none of these cases do the number of combinations of cell types, connections, tissue behavior, or descriptions preclude diagnoses, research or treatment.  A very small sample of this heterogeneity is suggested by the table below.  

Heterogeneity In Normal Functioning And Disease States In Human Biology (very partial list)

Endothelial cells	Diabetic nephropathy
Hematopoietic Stem Cells	Hepatitis C virus
Neuroendocrine Neoplasms	Ischemic Stroke
Leukemia - Clonal and Intraclonal cell types	Prostate Cancer
Aphasia syndromes	Mitochondrial Myopathies
Atrial Fibrillation Syndromes	Asthma
Immunodeficiency syndromes	Coriticobasal Degeneration
Diabetes Mellitus Type I and II	Viral Syndromes
Congestive Heart Failure	Cryptospridium genus and species

The authors ignore clinical heterogeneity that physicians have to address in their patients every day.  Very few physicians see clinical trials subjects as patients requesting assistance. That means comorbid physical illnesses, variations in patient tolerance of medical and psychological interventions, pharmacokinetic and pharmacodynamic factors, heart disease, liver disease, renal disease, substance use disorders, traumatic brain injuries, old age, pediatric age, suicide risk, aggression risk, impaired functional capacity, and even pregnancy have to be addressed in patients being seen every day by psychiatrists and adjustments have to be made. Only physicians schooled in heterogeneity would be able to treat those people.  Only physicians schooled in heterogeneity would realize that the people in clinical trials are rarely the people being seen in the office.  

In conclusion, the authors have a poor understanding of diagnostic heterogeneity and why it is a central part of medicine.  Some of their arguments are similar to arguments offered up by the critics of Kraepelin in the early 20^th century.  Other arguments - like the combinatorial ones reflect a poor understanding of biological systems and how they scale as well as a lack of understanding of medicine. Physicians know for example that diagnostic models are not completely explanatory, that over time - the explanations change, but that science exists at some level of that explanation or treatment. That is the nature of biological as opposed to physical systems. Anyone interested in these issues can find a rich literature out there that describes these problems and even the involved philosophy. Unfortunately, only one of the authors referenced (out of 28) is written by anyone authoritative in that area.

The only disappointment greater than an article like this being published is the fact that it was published in the journal Psychiatric Research.  It has little to do with psychiatry or research and it is shocking that the obvious problems with article were overlooked. On the other hand, this journal was never at the top of my reading list and this may be why.

George Dawson, MD, DFAPA

References:

1: Allsopp K, Read J, Corcoran R, Kinderman P. Heterogeneity in psychiatric diagnostic classification. Psychiatry Res. 2019 Sep;279:15-22. doi: 10.1016/j.psychres.2019.07.005. Epub 2019 Jul 2. PubMed PMID: 31279246.

2:  Black DW, Grant JE.  DSM-5 Guidebook. American Psychiatric Publishing, Arlington, VA: pp 543.

3: Feighner JP, Robins E, Guze SB, Woodruff RA Jr, Winokur G, Munoz R. Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry. 1972 Jan;26(1):57-63. PubMed PMID: 5009428.

4: Kendler KS, Muñoz RA, Murphy G. The development of the Feighner criteria: a historical perspective. Am J Psychiatry. 2010 Feb;167(2):134-42. doi: 10.1176/appi.ajp.2009.09081155. Epub 2009 Dec 15. PubMed PMID: 20008944.

5: Braun, V., Clarke, V., 2006. Using thematic analysis in psychology. Qual. Res. Psychol. 3, 77–101. https://doi.org/10.1191/1478088706qp063oa.

6: Kendler KS, Engstrom EJ. Criticisms of Kraepelin's Psychiatric Nosology: 1896-1927. Am J Psychiatry. 2018 Apr 1;175(4):316-326. doi: 10.1176/appi.ajp.2017.17070730. Epub 2017 Dec 15. PubMed PMID: 29241358.

7: Bell, L., 1849. On a form of disease resembling some advanced stage of mania and fever. Am. J. Insanity 6, 97–127. 

Happy Labor Day 2019

I decided to keep posting a Labor Day greeting to my fellow physicians. I’ve been doing this since 2013 and previously linked to all of those pages. Now there is a search feature in the upper right corner of this blog and you can just search on Labor Day if you are interested. My post this year is truncated based on the fact that very little has changed since my fairly comprehensive post 2018. If you will look up that post I comment on physician productivity, the EHR, pharmaceutical benefit managers, managed care and health insurance companies, maintenance of certification, and burnout in some detail. The advances in these areas have been too trivial to comment on in terms of either progress or the chronic lack of progress. I am sure that some organizations would like to debate that. The APA for example would point out that a health insurance company was successfully sued for failing to reimburse care for mental illness. The judge in that case actually made some fairly critical remarks directed at the managed care company, but on a day-to-day basis the average psychiatrist and the patients they are treating notice nothing but continued oppression.

Psychiatrists and their patients traditionally have fewer resources than other physicians and standard medical and surgical care. The overwhelming signs of this include jails being used as psychiatric holding tanks (I refuse to consider them hospitals) and the ongoing bed shortage. That bed shortage leads to overcrowding in emergency departments and a tendency for patients with mental illness to be the only ones discharged untreated from emergency departments. That often happens after they’ve been held there without treatment for days at a time.

There is something basically wrong with a government and political system that refuses to provide humane and equitable care for people with mental illnesses on the one hand and blames them for societal problems on the other. Just earlier today in the context of yet another mass shooting I heard the President describe the perpetrator as being “very mentally ill”. This occurred after a recent visit to the White House by a National Rifle Association representative. During that visit the president was talked out of advocating for universal background checks and the party line became “blame the mentally ill for mass shootings”.  It appears that the executive branch has a red line that they won’t cross when it comes to rational gun policy and a second red line that they won’t cross when it comes to providing equitable treatment for people with mental illness and addictions.

I think that is a relevant Labor Day observation for physicians because these irrational policies affect all of us. As psychiatrists we see very mentally ill people go in and out of hospitals and administrators pressure us to get them out before they are stable.  They are typically discharged to minimal outpatient services. We experience the tension of trying to get people off of inpatient medical and surgical units or out of the emergency department to appropriate psychiatric settings when there are none. Our physician colleagues feel that pressure. We all recognize that we were not taught to treat people this way in medical school. The only reason we do is that physicians no longer control the practice of medicine. Business administrators and people with no medical qualifications do control the practice of medicine. I repost the graphic here that was sent to me by David Himmelstein, MD who also gave me permission to use it on this blog.  Just getting rid of all of that bad management would result in saving a trillion dollars and bringing US health care costs in line with the country with the second highest per capita costs - Switzerland. 

It is clear to me that the problem with the physician work environment - the place we all labor intensely for too many hours - is a problem with administrators. Never before in the history of medicine have we had so many administrators telling us what to do. The graphic clearly illustrates that.  As working physicians we all know what that means.  We know it means when an administrator suddenly has a “great” idea that is not based on science or medicine and we all have to live with it for months or years. We all know what it means when a group of administrators suggests that we are not getting patients out of the hospital fast enough even when they are still ill.  We know what it means when we have a lengthy meeting with administrators for our “input” only to learn that they didn’t really want our input they just wanted to tell us how things were going to be for the rest of our career. And if you are as old as me, you might recall a time when medical departments were run by physicians and they had business managers who took care of business. In those days there were clear boundaries between medicine and business - not like it is today.  We are well past that point now.  The practice environment is a boundaryless morass of business people telling physicians, pharmacists, and patients what to do.  The rationale for this morass (cost containment) is no longer visible - probably becuase this model has failed miserably. Instead there are massive costs and a massive transfer of those direct costs to patients and indirect costs to physicians.

It has also resulted in the lowest possible quality of care.  The quality of medical care and how that is measured became a secondary consideration when businesses took over medicine.  A clear example is the treatment of depression on an outpatient basis. One of the standards promoted by the managed care industry is measurement based care using a scale like the PHQ-9 for ongoing assessment.  Unfortunately this process lends itself to using the measurement as a diagnosis and rapid route to treatment with antidepressants. Several approaches to depression including subsyndromal depression in primary care settings are ignored and PHQ-9 scores are followed as a measure of quality improvement.  This is the type of gross oversimplification that occurs when clinical medicine (1) is ignored in the context of businesses claiming that their measurement process is superior.

These inefficiencies in the day-to-day work of physicians are presented as improvements that we should all be happy to go along with.  In many cases administrative catch phrases like: "Change is good" accompany the poorly thought out and unscientifically implemented policies. The practice environment for physicians will only improve if the  bean counters no longer run medicine.

Until then Labor Day will be just that.

George Dawson, MD, DFAPA




Reference:

1: Arroll B, Chin WY, Moir F, Dowrick C. An evidence-based first consultation for depression: nine key messages. Br J Gen Pract. 2018 Apr;68(669):200-201. doi: 10.3399/bjgp18X695681. PubMed PMID: 29592945

Door County Summer Institute #33

The Door County Summer Institute (DCSI) was founded by Medical College of Wisconsin Professor Carlyle H. Chan, MD.  It is held at the Landmark Lodge in Egg Harbor, Wisconsin.  Egg Harbor is one of many small towns that dot the Door County peninsula bordered on the west by Green Bay and on the east by Lake Michigan.  If you have a lake view from the Lodge, there is generally an unobstructed view of the expanse of Green Bay with a few visible islands on the horizon. The weather this time of the year is tropical for the midwest with temperatures in the 80s and the occasional thunderstorm.

The DCSI is a psychiatry conference and most of the people who attend are psychiatrists but there are also psychologists, social workers, NPs, PA-Cs and nonpsychiatrist physicians.  The programs are very eclectic with topics ranging from psychopharmacology to terrorism. In the course I have attended there have been 1 to 3 instructors.  The instructors are all generally considered to be experts in the fields they are presenting. The courses are generally 2 days in duration (mornings only) with plenty of discussion about places to see in the area that include, restaurants, art galleries, concerts, plays, and musical productions.

As I mentioned in a previous post, I attended four sessions on Practical Neuropsychiatry for Clinicians presented by Sheldon Benjamin, MD.  I consider myself to be a neuropsychiatrist.  Early in my career, I attended behavioral neurology conferences and ran an Alzheimer's Disease and Memory Disorder Clinic co-staffed by a neurologist for about 12 years. I also evaluated neuropsychiatric problems in acute care settings. My hope was to get some complementary knowledge from an expert with a different career path and I was not disappointed.

The first session was spent on an overall neuropsychiatric approach to the patient and Dr. Benjamin made the observation that neuropsychiatry is personalized medicine in that each formulation is uniquely developed for the individual and it also answers the question about what treatment will help that unique individual. On that basis, is is not a nonspecific label.  His reasoning can be extended to the psychiatric formulation in general. As previously noted on this blog, a formulation is the most unique aspect of the evaluation and it needs to be included as well as the diagnoses. Any psychiatrist knows that people with the same diagnoses are unique individuals and that the diagnosis alone does not take into account the unique conscious states of individuals any more than any other medical diagnosis.

From there most of the rest of the first day was spent on a discussion of frontal lobe function and executive function.  Rather than focus on the consensus list of neuropsychological tests thought to comprise executive function, he presented an adaptation of D. Frank Benson's schema to illustrate the basic dimensions (anticipation, monitoring) involved in goal selection and planning and the underlying behaviors.   He emphasized the assessment of frontal function as being possible without any specialized testing and illustrated the point with a humorous example (1).  Executive function was primarily a product of prefrontal cortical function but parietal cortex and cerebellar cortex were also involved on the basis of an analysis of cognitive and neuroimaging articles (2).

There was an emphasis on practical assessment frontal lobe function and more specifically the ecological validity of the tasks. In other words what do the tests mean in real life. The MoCA Test was used to illustrate that tests of frontal executive function do not require any special equipment. The trail making, clock drawing, and verbal fluency sections were highlighted as requiring frontal executive function. The MoCA Test was described as potentially problematic due to the new licensing procedure. Dr. Benjamin presented several other tests that could be added to the bedside exam that included both neurological examinations of for example anti-saccades and more complex cognitive tasks such as complex problem-solving, inferential reasoning, the script generation task, and a headline task. After the presentation there was a brief workshop where patient was presented and participants needed to pick one behavioral problem, develop a hypothesis, and suggest what tests could be used.  The ultimate goal was to consider not just a useful test, but also potential rehabilitation approaches. A total of 16 cognitive domains and 30 cognitive tasks were provided that could be used to develop specific tests.

The final section of the first two days was about traumatic brain injuries.  I have a previous post on an application from this section on classifying the severity of these injuries.  The epidemiology is striking with a prevalence equivalent to patients with severe mental illnesses.  The death rate is about 50,000 people per year and at 1 year a many as 15% of people with a mild TBI remain symptomatic.  The myth discussed is that we all grow up thinking that TBIs are relatively benign.  I see that occurring regularly in the patients I assess who have had multiple TBIs or concussions and who never saw a physician for assessment. In many cases they resumed playing the sport immediately where they were injured.  That is a very high-risk scenario.  The coupe-contre-coup injury was discussed as well as how to identify it on brain imaging studies and autopsies.  Several specific mechanisms of injury were discussed including diffuse axonal injury (DAI) and how that occurs during TBIs.  Shear forces used to be considered the main mechanism of injury but now permeability changes are thought to occur that leads to lysis of axons in the 12-24 hour window.

Second Syndrome or Second Impact Syndrome was mentioned as a complication of returning to play too soon and sustaining a second concussion with a resulting massive injury.  It apparently based on a 1984 report (3) where a football player sustained a concussion in a fight and then another concussion 4 days later playing football.  That second injury resulted in massive cerebral edema and death. The purported mechanism is a vulnerable window of decreased brain metabolism.  Concussed athletes have been examined with MR spectroscopy.  In this method, N-acetylaspartate (NAA) is a marker of neuronal viability. Following concussions, NAA is depressed to the lowest at about three days after the injury and it recovers by 30 days.  In another study, if a second injury occurred before 15 days – recover of the NAA marker did not occur until 45 days.  Some sources consider this syndrome to be controversial due to recall bias and a lack of reported cases in other literature, but the depression of brain metabolism is concerning.  Clinical symptoms of TBI may be underreported or not reported at all during this recovery phase.

In the section on specific frontal syndromes, Dr. Benjamin pointed out that he was pleasantly surprised by the Neurocognitive Disorders section in the DSM-5.  I agree with his observation. There is highly detailed information about making those diagnoses and what information is relevant. For the course he looked at personality changes associated with various frontal syndromes such as orbitofrontal syndrome, prefrontal syndromes, mixed frontal syndromes, ventromedial syndromes, and secondary mood disorders.

That last two days of the course were focused on memory, encephalitis lethargica, autoimmune syndromes, and the six landmark cases necessary for neuropsychiatric literacy.  I will end with a summary of the six cases because for most readers of this blog – they are readily accessible in the paper written by Benjamin, et al (4).  His discussion of the Phineas Gage case was remarkable given the amount of misinformation that exists.  He presented a detailed timeline of the injury and how Gage was treated initially by the town physician and then by the railroad physician.  New England Journal of Medicine subscribers may be surprised to learn that they have access to the full text of an 1848 account from attending physician Dr. Harlow (5).  There are 43 references in the medical literature. For anyone not familiar with the case, he sustained a penetrating wound to the brain when a 43 inch, 13.5 pound iron rod used to tamp sand and gunpowder into a hole for excavating rock was propelled through his left orbit and left frontal lobe exiting out the top of his skull.  Dr. Benjamin pointed out that there are numerous false accounts of the incident and I had read several suggesting that the rod had to be extracted from Gage's skull by the doctor in attendance. In fact, the rod blew through his head an landed about 30 feet away.  The rod had been specially designed by Gage so that one end was tapered for prying.  That is what led to the penetrating wound and is also what saved him.  The year of this injury was 1848, before antibiotics and neurosurgery.  Gage was transported to a hotel where he stayed and was able to walk up to his room on the second floor where he experienced transient delirium but he was able to recover and return home after 74 days.  There are numerous accounts of his neuropsychiatric recovery.  The commonest description is that he was "no longer Gage".  He could no longer work as a railroad foreman, but sometime later traveled to Chile where he was a stagecoach driver managing a 6-horse stagecoach. He died about 12 years after the injury from status epilepticus.  The index case of severe frontal lobe damage illustrates preservation of cognitive and motor skills with some personality changes.        

  

 In conclusion, I highly recommend Dr. Benjamin’s work and this course if you ever want to attend a DCSI.  More to the point, I highly recommend that medically oriented psychiatrists develop skills in neuropsychiatry by working these principles and skills into their practice like I have over the past 30 years.  When I say medically oriented psychiatrists, I am generally referring to acute care psychiatrists (inpatient, addiction and consultation liaison) and outpatient psychiatrists who are seeing patients as identified as having cognitive problems and possible dementias like geriatric psychiatrists or psychiatrists who specialize in treating people with complex medical and psychiatric problems. In my situation seeing inpatients with a variety of complex problems, making associated medical diagnoses, and working closely with other consultants was very effective in reaching this goal. An additional skill was reading all brain imaging and taking an early interest in EEG and QEEG.  Seeing all of the brain imaging of patients has never been easier than with the current EHR.  When we were using only paper records, I would often trace an axial section of a CT or MRI and put that in the patient’s chart but now it is right there.   I think it is also a critical factor in deciding what an ultimate practice environment must look like for psychiatrists interested in this type of practice. Th environment has to provide access to the necessary imaging, neurophysiological, and laboratory testing as well as easy access to other consultants.  Complex problems require an environment where they can be addressed.  Many current practice environments for psychiatrists do not provide access to these tools or state-of-the-art treatment modalities.  In many of these settings it is difficult to find a working blood pressure device. 

Given the appropriate medical setting, there has never been a better time to be a neuropsychiatrist and train neuropsychiatrists for the future.

George Dawson, MD, DFAPA

References:

1: Rockwood K, Chertkow H. A cellular-telephone model of assessing frontal lobe function in physicians. CMAJ. 2007 Dec 4;177(12):1533-5. PubMed PMID: 18056616. Link (full text)

2: Nowrangi MA, Lyketsos C, Rao V, Munro CA. Systematic review of neuroimaging correlates of executive functioning: converging evidence from different clinical populations. J Neuropsychiatry Clin Neurosci. 2014 Apr 1;26(2):114-25. doi: 10.1176/appi.neuropsych.12070176. Review. PubMed PMID: 24763759. Link (full text)

3: Kamins J, Giza CC. Concussion-Mild Traumatic Brain Injury: Recoverable Injury with Potential for Serious Sequelae. Neurosurg Clin N Am. 2016 Oct;27(4):441-52. doi: 10.1016/j.nec.2016.05.005. Review. PubMed PMID: 27637394; PubMed Central PMCID: PMC5899515. Full Text

4: Benjamin S, MacGillivray L, Schildkrout B, Cohen-Oram A, Lauterbach MD, Levin LL. Six Landmark Case Reports Essential for Neuropsychiatric Literacy. J Neuropsychiatry Clin Neurosci. 2018 Fall;30(4):279-290. doi: 10.1176/appi.neuropsych.18020027. Epub 2018 Aug 24. PubMed PMID: 30141725.

5. Harlow JM.  Passage of an Iron Bar Through the Head. The Boston Medical and Surgical Journal. 1848 XXIX(20): 389-393.

6: Damasio H, Grabowski T, Frank R, Galaburda AM, Damasio AR. The return of Phineas Gage: clues about the brain from the skull of a famous patient. Science. 1994 May 20;264(5162):1102-5. Erratum in: Science 1994 Aug 26;265(5176):1159. PubMed PMID: 8178168.

7: Haas LF. Phineas Gage and the science of brain localisation. J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):761. PubMed PMID: 11723197; PubMed Central PMCID: PMC1737620. Full Text

Supplementary 1:

Don’t forget Dr. Benjamin’s Brain Card as an excellent resource.  The nominal cots is used to fund a web site that provides free access to additional clinical resources that are available to Brain Card holders for free.

Supplementary 2:

I anticipate some complaints from psychiatrists who will say that they do not have enough time to do detailed assessments like the ones suggested in this post.  Despite the penetration of managed care and the fact that most physicians are employees, I contend that it is still possible to do detailed and intensive evaluations on patients with complex problems. My strategy for a long time was to do inpatient work where I could see people as many times a day as I needed to an I had access to resources like EEG labs and imaging studies.  The ability to meet with families for a more in depth analysis of the problem was also a plus. Choosing the correct work setting goes a long way toward allowing this kind of work.  

The Last High School Reunion

I just went to my last high school reunion.  The reunion model in my hometown is apparently changing so that graduates from all years will meet every 5 years - rather than just meeting with your specific class cohort.  Reunions have a lot of stereotypes.  Hollywood produces a fairly consistent revenge of the nerds on the cliques that suppressed them theme.  Real life is hardly ever that  clearcut.  I have limited experience with reunions myself.  I went to one other reunion about 20 years ago.  I spent most of the time talking with two of my classmates who were farmers and looked forward to seeing them again.

My high school class was moderate in size by today's standards - 230 people.  Twenty per cent of my classmates have died.  As I looked at that list I was reminded of the first girl that I ever slow danced with in the 8th grade. I was reminded of the girl who had an outstanding sense of humor and who could always make me laugh.  She was always in a good mood and I was always happy to see her.  I was reminded of the guy I was always paired with in gym class for wrestling who was about four times stronger than me and and who could wrap me into a knot. I remembered the girl in my homeroom who was just in front of me in alphabetical order every day when they took attendance.  I remembered the guy who was killed in a fight in college and what a tragedy that was.  I have been thinking about him a lot over the past 48 years.

My association to personally knowing almost everyone on that list is a comment that one of my psychoanalyst supervisors made when I was in training.  He asked me what I thought about learning that someone I knew had died.  I was a very neurotic kid and had significant death anxiety from an early age and my response was: "It could have been me." He told me that I was wrong and gave me what I considered to be a more narcissistic response: "Better him than me!"  Over the decades since, I have tracked that response and most of the time my original response is the first one I think of. But that is complicated when you grow up and mature with a group of people. I know that I was not always at my best in terms of social interactions but I can also recall being bullied and punched and intimidated like most people in school. What happens when you learn of the death of one of your antagonists from middle school or high school?  It turns out to be more complex, but at this point in life it does not matter.  I feel badly about anyone who does not make it to retirement.  I am at the disadvantage of being trained as a psychiatrist - so I don't know what it is like for other people.  Physicians are trained to save lives and psychiatrists are trained further to know that only a relatively primitive person rejoices in the death of another.  But more significantly, even the bullies change over time often to the point that they are not recognizable from their high school behavior.

At the previous reunion that I attended, I walked past a guy who I knew and he knew me. He probably remembered me from high school and all of the associated baggage as well as I remembered him.  We walked past each other several times that night and made eye contact but never spoke. Several years later I was out cycling and decided to pull into the cemetery to see if I could locate my father's headstone.  He would have been dead about 37 years at that point.  I found it and noticed that just to the left was the headstone of a good friend from high school and college.  To the left of that was the guy from the reunion that I never talked to.  His gravestone sat in a field of gravestones with his family name.  I can recall my father talking about people with that family name. Our families were from the same part of town and they did the same kind of work and yet 30 years out of high school there was something lingering there that kept us from acknowledging our common roots. That kind of put things in perspective and I was determined not to let that happen again.

A critical issue is that we know a lot more about human development than we did 30 years ago. I know that as well as anybody both professionally as well as personally.  Looking back on my life in  late high school and early 20 years - I recall feeling like I was in a fog. I could not think very clearly and spent a lot of time daydreaming and fantasizing. I had limited social skills and compensated by avoiding social interactions. The blue collar culture that I was raised in taught me to be suspicious of authority figures - especially politicians and business and union leaders. Some time in my late 20s - I came out of the fog. I would never have guessed that my profession would eventually involve intense interpersonal interactions with people all day long.     

My personal experience starts with the fact that I am an introvert.  It might not come across in the writing on this blog, but conversation with me invariably includes a lot of long pauses unless you are filling in the dead air.  Nobody would consider me charismatic.  I am very comfortable being by myself for long periods of time without social contact.  I don't seek out social contact, and often don't signal people that I am in the area and ready to engage them in conversation. For the past 5-10 years there have been arguments raging about the introversion-extroversion dimension and the relative merits and faults of each.  My real world experience is this dimension really exists but it is more complicated than the stereotypes. For example, introverts are not avoidant and are comfortable in social situations.  They are just not conversationalists and are not engaging. In my case for example, I have no problem at all talking with people all day long about the intimate details of their life.  I have no problems giving hundreds of lectures to medical students, residents, and other physicians.  On the other hand, at a residency graduation celebration - one of my residents came up to me and asked me if I was trying to hide behind the drapes in the ballroom.

The good news is that the reunion went very well. Contrary to the stereotypes, everyone seemed grateful to be there.  Several people had medical and psychiatric close calls that they shared with me.  And I am using close calls the way Carl Sagan did in the Demon Haunted World - without emergency medical or surgical intervention they would not have made it.  Retirement was probably the next most common topic that I discussed with classmates.  The majority of people I talked with were retired, happy to be retired, and either inquisitive about why I am not retired or actively trying to talk me into retiring.  One of the considerations I did not mention to anyone is that I still have not worked as long as they did before they retired (about 35 years) but would be getting there in another couple of years.

The most interesting conversations occurred with people who I have known the longest even though I have not seen them in decades.  We talked about past times, what we had done in the past, and what we planned for the future. I was reminded of the fact that some of these folks knew where I lived as a kid, came over to that house, and did things like play chess and work on models. We did these activities in an odd part of my parents house at the top of a stairway.  Based on what my friends had accomplished, I was reminded that they were bright, creative, and inquisitive people.  They had accomplished a lot and successfully raised families.

On the topic of children and grandchildren - it was clear that the next generation had identified with their parents (my classmates) as evidenced by their vocational choices or choice of hobbies and pass times. Spending time with grandchildren was given as one of the reasons for happiness in retirement.

The physical environment of the reunion was carefully developed by the committee.  The food was buffet style and excellent. Decorations were tasteful and historically meaningful with hippie themes.  This reunion coincided with the 50th anniversary of Woodstock.  There was some barely audible surfer music playing at one point that faded out and no more music was heard.  At the 30th reunion, there was loud disco music at one point and only one couple disco dancing.  I think the committee realized that at 50 years - talking is more important than dancing.

I don't think I have anything profound to say about reunions. anything that I observed there I have seen in life many times before. As people get older,  they are more reasonable. There was some concern about political discussion going into it and an informal ban.  I violated that by talking with a friend who was a political activist until recently - but he said that after years of involvement that he was burned out - much less interested.  Apart from that discussion - politics and other provocative topics were not mentioned at all.  I thought about my prevailing model of a successful society. People just want to work and make it home safely to their families at night.  I saw nothing at my reunion to counter that idea, but it was clear that the retirees maintain a family focus in retirement and do what they can for the next two generations.

Was I successful in countering my introverted tendencies?  I think that I was to a large extent.  I talked to most people that I made eye contact with. I talked to some people more than I probably have to date on that night. I am sure that talking to people on a daily basis for over 30 years has changed me to some extent. My experience at the previous reunion led to a conscious change.  There were probably more opportunities, but at some point there was equilibrium in the room and small groups had formed where people were probably talking with those who they were most comfortable talking with.  I was not perfect by any means.  The room had a view of Lake Superior and a breakwall with a lighthouse on the western end. At one point when the conversation had bogged down - I looked out there and saw a speedboat cruising along the distant side of the breakwall. I watched the boat for a few minutes and projected myself out there and then snapped out of it and came back to reality.

My two farmer friends from the previous reunion never showed up and there were other people that I missed.  Once you have lived a whole life out of high school it seems that those important people go in an out of your life very quickly. A good friend of mine from my class was in town a few months earlier and got my email address from my brother.  When I heard he was looking for me - I tracked him down on LinkedIn and sent him a message.  He was not at the reunion and has not contacted me.

It was a good reunion. I liked being a part of this generation  and some of its subcultures. I was with most of these people in one capacity or another for at least 5 years and and 5 of us were together since kindergarten.  Personality change is gradual even with an early boost from developmental neurobiology.  For me a moderate amount of change has only taken about 50 years. 


George Dawson, MD, DFAPA


Supplementary:  My wife who is an extravert who can talk with anybody gave me high marks for interaction at the reunion.  That is as close to an objective review as I can get.