Sunday, November 27, 2016

Mechanism Of Action Of Lithium - A Brief History

As a chemistry major and a psychiatrist Lithium has a special place in my consciousness.  During the years that I took organic chemistry lithium aluminum hydride was a favorite reducing agent when creating certain organic syntheses.  Most chemistry majors remember metallic lithium as one of those highly reactive metals that was packed under oil to prevent contact with water or even moisture in the air.  Lithium's reactivity is why the free metal does not exist in nature.  The most common form used as a medication is lithium carbonate in various preparations.

There has been a lot of speculation about the mechanism of action of lithium since its discovery.  Early in my career the definitive source of information for all things lithium-related was the Lithium Information Center at the University of Wisconsin Department of Psychiatry.  It was possible to call them and ask them anything about lithium and get the relevant references sent to you.  They also produced the Lithium Encyclopedia for Clinical Practice.  The mechanism of action was described as unknown at the time but ongoing research was cited (p. 7) in "ion substitution with subsequent effects on amine metabolism, membrane transport, glucose metabolism, and neurotransmitter synthesis and degradation."  An entire chapter was dedicated to mechanism of action.  In that chapter, the review of what was known about the mechanism of action at the time is interesting.  The major neurotransmitter systems being studied at the time were catecholamines, serotonin, and acetylcholine.  Animal studies showed acute changes on norepinephrine turnover that was only slight to non-existent with chronic use.  Results on serotonin turnover were conflicting, but it prevented hyperaggressive behavior resulting from a serotonin depleting compound that blocked tryptophan hydroxylase (parachlorophenylalanine).  Acute administration did not alter dopamine turnover.  Chronic administration resulted in increased turnover in mesolimbic and striatal areas but not the cortex.  These observations led to theories that lithium worked by altering post synaptic receptor sensitivity including decreased beta adrenoreceptor effects, stabilized opioid receptors, and preventing dopamine receptor hypersensitivity.

There was some speculation about endocrine mechanisms since it was known that lithium blocks release of thyroid hormone (T4).  It was also believed to reduce testosterone levels as a possible role in the anti-aggressive properties of the medication.  Studies at the time showed that in patients treated for aggression and closely followed, they had increased levels of luteinizing hormone but normal testosterone levels.  A significant theory at the time was that lithium worked by reducing T4 levels and this reduced beta-adrenoreceptor potentiation in mood disorders.  Lithium was also thought  to possibly work by the effect it had on the intracellular concentration of other ions like sodium, calcium, potassium, and magnesium in neurons. The 1980s was a decade when research interest on cell signalling was becoming more widespread after Sutherland's Nobel Prize for the discovery of cyclic AMP (cAMP).  Lithium was noted to inhibit adenylate cyclase the enzyme that produces cAMP.  Specific forms linked to beta-adrenoreceptors and prostaglandin-E1 were noted to be blocked leading to speculation that these mechanisms were related to mania.  

Another definitive source of drug mechanisms over the same era was The Biochemical Basis of Neuropharmacology.  My collection of these texts starts in 1984 with the fourth edition of that text.  There was a single paragraph on the action of lithium and its effect on catecholamines.  They used the term facilitated recapture mechanism (2) suggesting that the overall block  of stimulus related norepinephrine (NE) release may be due to facilitated uptake of NE.  They also point out the difference in acute and chronic effects with supersensitive NE responses with chronic administration.  By the fifth edition of this text (3), the speculative mechanisms had expanded to include inhibiting inositol-1-phosphatase in the phosphoinositide pathway (p. 114), the same NE mechanism as the previous edition (p. 306), and a new observation that lithium facilitates tryptophan uptake initially but with chronic administration tryptophan production normalizes despite increased uptake due to decreased enzymatic conversion to serotonin (5HT).  Shifting the balance between synthesis and uptake was suggested as a more stable mechanism.  By the seventh edition, lithium was back to being mentioned on single page  as part of the larger discussion of deficits in the catecholamine hypothesis of mood disorders - a theme the authors started in the fourth edition.  By the eighth and final version of this text there was no mention of lithium at all.  Two of the authors were involved in a successive text called Introduction to Neuropsychopharmacology (5).  That text describes lithium as "one of the major achievements of psychopharmacology of the past 50 years (p. 321).  The authors acknowledge that the mechanism of action remained unclear but the theories included inhibition of inositol monophosphatase, inhibition of glycogen synthase kinase-β, and modulating g protein function (p. 321).

Another excellent source of the evolution of lithium theory was the American College of Neuropsychopharmacology's (ACNP) Generation of Progress series.  The series has been discontinued.  I have the third to the fifth editions and the most substantial section on lithium action was in the Fifth Generation of Progress (6).  This chapter begins with an overview of the time course of mood stabilizer action and how the focus had changed over the previous 20 years from changes in neurotransmitter release and regulation to changes in cell signalling and morphological changes consistent with "altered signalling in critical regions of the brain."  The chapter is an overview of the complex effects of lithium on ion transport, neurotransmitter release, signal transduction, circadian rhythm, gene expression, and neuroplasticity.  The data showing that lithium and in some cases valproate and carbamazepine can regulate gene expression via transcription factors is reviewed.  Some of the changes produced a neuroprotective effect against a number of factors and at about that time neuroprotection was considered a potential positive effect form both mood stabilizer and antidepressants.  It was very interesting to reread the section on neuroplasticity.  Lithium was known to be an inhibitor of glycogen synthase kinase-3 beta (GSK-3β).  This molecule is a component of the wnt signalling pathway (see diagram).  This inhibition results in reduced phosphorylation of tau protein and the overall effect of  increased microtubule assembly.  Phosphorylation of MAP-1β is also inhibited by lithium and this results in increased axonal spreading and increased growth cone area and perimeter.  Long term down regulation of protein kinase C (PKC) substrate myrisolated alanine-rich c-kinase substrate (MARCKS) via phosphoinositide signalling was also shown to MARCKS expression is high in developmentally important structures like neuronal growth cones necessary for brain development.  It is also high in limbic structures in the human brain that retain the potential for plasticity - like learning and memory.  The authors conclude that section by pointing out that by its action on PI/PKC and GSK-3β signalling cascades, lithium "may alter presynaptic and post-synaptic structure to stabilize aberrant neuronal activity in critical areas of the brain involved in the regulation of mood."  In the space of just a few years, lithium was suddenly implicated in neuroplasticity and neuroprotection.  Maybe the Decade of the Brain did produce some benefits?  

That brings me to the latest piece of the puzzle.  A paper from Molecular Psychiatry (7) this October further examines the role of these signalling systems and how everything comes together.  The authors propose that one common biochemical pathway that may confer susceptibility to psychiatric disorders is the Wnt/ β-catenin pathway.  This is a pathway that is critical in all multicellular organisms for cell differentiation, growth, proliferation and morphology across a number of organ systems.  At least part of the pathway has a direct influence on the cytoskeleton.  It has been implicated in human diseases especially tumors and the metabolism of tumors.  The pathway was discovered about 34 years ago.  The  authors also looked at DIX domain containing-1 (DIXDC1) as a cytoplasmic transducer of the Wnt/ β-catenin pathway.  DIXDC1 interacts with disrupted in schizophrenia-1 (DISC-1) gene that has been implicated in the genetics of schizophrenia, bipolar disorder, and autism spectrum disorder.  DIXDC1 also has a restricted distribution in the nervous system depending on developmental stages.

Like most modern papers this article has an intense experimental section.  The authors prepared a DIXDC1 knockout mouse model and looked at several experimental manipulations.  They used several behavioral pharmacology approaches to model anxiety, depression, and social interaction among the mice.  On these models the Dixdc1KO (knock out) mice showed increased depression, increased anxiety, and less socialization than the Dixdc1WT (wild type) mice.  These behavioral phenotypes correlated with histological changes and the Dixdc1KO mice had reduced spine density and an increased number of filopodial or immature spines on pyramidal cell dendrites.  The authors confirmed that these reduced spine neurons functioned in an electrophysiologically expected manner.  They analyzed the reduced spines in the Dixdc1KO mutants and found that there was a decreased density of glutamatergic synapses along the dendrites of pyramidal neurons.  In order to determine if the Dixdc1KO Wnt/ β-catenin pathway would be impaired by the loss of cytoplasmic signal transduction proteins.  They found that treating the KO and WT neurons with and activator (Wnt3a) - the  level of β-catenin rose as expected in the WT neurons.  Wnt3a also failed to effect spine maturity or glutamatergic synapse density on the KO type neurons.

Most importantly for psychiatrists, the authors hypothesized that lithium would correct both the behavioral phenotype and structural defects in the Dixdc1KO type mice by inhibition of GSK3.  Injection of lithium or the specific GSK inhibitor GSK3i corrected the behavioral phenotypes and spine density, spine morphology, and glutamatergic synapse density in the pyramidal neurons of Dixdc1KO mice.                        

In a separate experiment the authors looked at a large database of patients with psychiatric disorders.  The first database contained 6000 cases of autism spectrum disorder (ASD) and 7000 controls.  The ASD cases had a greater number of sequence disrupting single-nucleotide variants (SNVs) that were judged to be likely to disrupt DIXDC1 function.  They showed the same pattern in patients with bipolar disorder (BD) and schizophrenia (Scz) versus controls.  In the end they had 4 patient data sets totaling 9000 cases (versus 11000 controls) with significantly more rare sequence disrupting SNVs.

The authors also used a cell based Wnt/ β-catenin signalling assay (compared to WT) to test specific missense SNVs from both psychiatric patients (BD, Scz) and ASD patients.  They found that rare missense SNV from ASD patients either increased or decreased Wnt/ β-catenin pathway activation.  Rare missense SNVs from psychiatric patients did not rescue spine density and synaptic deficits but the WT did.  A number of Wnt/ β-catenin pathway hyperactivating SNVs cased the expected decreased spine density, decreased glutamatergic synapse density and increased immature spine density.

The authors conclude that there may be other mechanisms in play that they could have missed.  They cite a downstream mechanism that is independent of the Wnt/ β-catenin pathway that leads to the structural changes they monitored in this study.  There are also different isoforms of DIXDC1 - some more active than others.  They do a great job of summarizing 20 years of research in the following lines:

"Several different biochemical mechanisms have been proposed to underlie the anxiolytic, antidepressant and mood stabilizing properties of lithium, a drug whose systemic use in modern psychiatry began in the first half of the last century.  Lithium's best validated mechanisms of action are inhibitory on IMP and INPP1, central phosphatases in the phosphoinositide pathway and on GSK3, the central kinase in the Wnt/ β-catenin pathway and AKT pathways."  (p. 8).  

 The story of lithium is similar to a lot of stories in biomedicine.  Research on lithium reflects a lot of popular theories of the day rather than any particular unique theory by one scientist.  That says a lot about the difference between physical sciences and biological sciences.  The technique of applying the most popular theories and lab techniques at the time is still common in medicine and neuroscience.  Like most neuroscience there needs to be further testing, replication, and debate about this mechanism but it does seem to be a lot clearer now than at any time in the past.  If the mechanism does check out there may be more than the few applications that currently involve lithium.  A lithium like effect from safer medications is potentially a very interesting one.  Applications may be as diverse as treating addiction - where glutamatergic innervation is thought to be an important component of top down control from the frontal cortex to neurodegenerative disorders and neuroprotection of synaptic complexity.

George Dawson, MD, DFAPA


1:  James W. Jefferson, John H. Griest, Deborah L. Ackerman.  Lithium Encyclopedia for Clinical Practice.  American Psychiatric Press,  Washington, DC; 1983.

2:  Jack R. Cooper, Floyd E. Bloom, Robert H. Roth.  The Biochemical Basis of Neuropharmacology.  4th ed. Oxford, England: Oxford University Press, 1982: 214.

3:  Jack R. Cooper, Floyd E. Bloom, Robert H. Roth.  The Biochemical Basis of Neuropharmacology. 5th ed.  Oxford, England: Oxford University Press, 1985: 115, 306, 319.

4:  Jack R. Cooper, Floyd E. Bloom, Robert H. Roth.  The Biochemical Basis of Neuropharmacology.  7th ed. Oxford, England: Oxford University Press, 1996: 490.

5:  Leslie L. Iverson, Susan D. Iverson, Floyd E. Bloom, Robert H. Roth.  Introduction to Neuropsychopharamcology.  New York, New York: Oxford University Press, 2009: 321-322.

6:  Robert H. Lenox, Alan Frazer.  Mechanism of action of antidepressants and mood stabilizers. In:  Davis KL, Charney D, Coyle JT, Nemeroff C, eds.  Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia, Pennsylvania: Lippincott, Williams, and Wilkins, 2002: 1139-1163.

7:   Martin PM, Stanley RE, Ross AP, Freitas AE, Moyer CE, Brumback AC, Iafrati J, Stapornwongkul KS, Dominguez S, Kivimäe S, Mulligan KA, Pirooznia M, McCombie WR, Potash JB, Zandi PP, Purcell SM, Sanders SJ, Zuo Y, Sohal VS, Cheyette BN.  DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling.  Mol Psychiatry. 2016 Oct 18. doi: 10.1038/mp.2016.184. [Epub ahead of print] PubMed PMID: 27752079.

8:  Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E. The way Wnt works: components and mechanism. Growth Factors. 2013 Feb;31(1):1-31. doi: 10.3109/08977194.2012.752737. Review. PubMed PMID: 23256519


Wnt signalling pathway is from VisiScience and their ScienceSlides 2016 slide set.

Tuesday, November 22, 2016

The Fake News

I have been watching the controversy about "fake news"with amusement.  The clamor is a direct product of the unexpected results in the Presidential election.  In search of somebody to blame, the media is currently pointing fingers at Google and Facebook as incentivizing a process where any group of people can write fake news stories, have them published and generate ad revenue from both of those services.  An expert in Big Data pointed out (1) that this is a problem with algorithms and suggested hiring human judges of fake news.  That will help until we hit the artificial intelligence singularity - a point at which humans will have access only to the news that our machine overlords want us to have.  But isn't the fake news about a lot more than just software?

Looking at the literal definition. there are different types of fake news.  Satire is the best example.  It is a staple of late night television comedy and satirical publications.  Implicit in this comedy is the capacity of the viewer to recognize immediately that it is fake and "get" the associated irony.  For various sub-populations who have difficult with social cues that may not be possible.  There is what used to be called propaganda or fake news with an agenda to control access to what information people have access to or how they think about it.   The implicit aspects of current fake news is that it is there to intentionally deceive but also profit by the structure of social media sites.      

Like most news cycles, this is another story that strikes me as absurd at several levels.  First off, how hard is it to look at your Facebook feed and realize that some of the sources being posted by people with too much time on their hands are the equivalent of an e-mail attachment from an unknown source?  The Wild West nature of the Internet prevents me from making up websites for fake news.  The first 5 that I made up apparently exist.  Suffice it to say that even a slight amount of Internet common sense should preclude a lot of these stories from consideration.

Secondly, is the concept of fake news really news to anyone?  I can recall arguing with my late father back in the 1970s about a book that was basically a collection of conspiracy theories about how one party or the other lost due to groups of powerful Kingmakers who were manipulating the electorate (sound familiar?).  But nothing slows down the outrage crescendo like publishing detailed and tedious theories in a book.  Immediate viewing by thousands of the outraged and outrageous creates a much better mob atmosphere.  The theme of a clueless electorate being manipulated in one direction or the other is a historical theme in America and probably most legitimate elections in the world.  Don't like my candidate - you must be clueless.  My candidate loses - I am going to ignore confirmation bias (among others) and write obsessively about why I think that happened.  I won't let any facts get in my way.  That basic process occurs whether or not there in an Internet or a Facebook or a Google.  The indignant losing side will always try to tip the landscape to their advantage in the future.  It is how we ended up with left and right wing media outlets in the first place.  It is basically why the United States has no politically viable third parties.

Thirdly, most of what passes for credible scientific news is in a way fake news.  Ioannidis has famously stated that most published research is false due to the inherent practical limitations of research scale and confirmation bias (3).  His observation matches my experience over the past thirty years and I have posted some famous examples on this blog.  A lot of this information is vetted more rigorously than anything that you will find in the popular press and of course the researchers are generally not conscious of the falseness of their research.  It turns out that is even true for the hallowed meta-analyses and what has become the cottage industry of statistics (4).  That same study estimates that only 3% of these studies are useful and there is a very large non-publication bias.

Fourthly, a lot of psychiatric fake news involves government spin to make the government and policy makers look good.  It coincidentally maintains a business structure that adds no value but extracts a lot of revenue from the system for "managing" care.  I have many posts that illustrate this fact.  Most recently, the Surgeon General's report would have you believe that the sad state of addiction treatment in this country had something to do with the fact that medical providers were ill equipped to treat addicts and they were just shuffled off to other community agencies.  That is very positive spin considering long standing policies by governments and their proxies to not pay for addiction treatment or in some cases the physical trauma effects of acute alcohol or drug intoxication.  That has been 30 years of rationing policies that were supposed to be stopped by parity legislation.  But that did not happen.

Fifthly, does it make sense to separate bullshit from lies in the fake news category?  Harry Frankfurt's essay on the matter ads some perspective.  Are the producers of what people consider to be fake news - liars or bullshit artists or both?  A relevant question from a technical perspective.  Is fake news just part of the abundant bullshit that Frankfurt suggests is "one of the most salient features of our culture."  Are the people who want to stomp out fake news just deniers of the level of bullshit that we each have to negotiate every day?  Frankfurt's observation, that I happen to totally agree with - is given below:

"The realms of advertising and of public relations, and the nowadays closely related realm of politics are replete with instances of bullshit so unmitigated that they can serve among the most indisputable and classic paradigms of the concept." (p. 22)

It may be that the indignant are just angry that somebody has found another way to make money off of bullshit that they did not think of or have access to.

Sixthly, psychiatry gets more than its fair share of fake news and again - a lot of that has been posted here.  I can say without a doubt that one of the largest fake news stories of 2015 was all of the fake news about the DSM-5.  Apocalyptic visions of what would happen when that book was released.  The horror of grieving patients being treated with antidepressants like they have been for decades by their primary care doctors.  The horrors of "medicalization" and "diagnostic proliferation".  The horrors of clueless psychiatrists and family physicians as helpless as Manchurian candidates against the hegemony of the DSM-5.  The philosophical horror of a manual with an implicit moral agenda about how people should live.  And it is written by (gasp) psychiatrists.  We cannot allow that to happen!   And of course the vast profits to be made on the diagnostic manual.  What really happened is best captured by a brief conversation I had with another specialist just  yesterday.

MD:  "Is there a reference that explains what happened to the personality disorders in DSM-5"
Me:  "Yeah there is a reference or two.  The organization is different but there is still a categorical approach to the major ones.  You don't really read the DSM-5 do you?'
MD:  "No - the codes are basically the same.."
Me:   "More importantly when you type "depression" into your EHR don't you get about 240 diagnostic codes..."
MD:  "At least - it depends what the default is set at."  
Me:  "That's my point.  Any general psychiatric diagnostic category in an EHR generates more diagnoses than are included in the DSM, even though the recent edition had fewer codes than the last edition.  And the only thing that counts are the ICD codes that phrase is attached to."

That is the reality of the fake DSM-5 news.  Just to be clear - no cataclysmic events. No moral collapse.  No willy nilly assigning diagnoses to people randomly on the street.  No primary care physicians changing what they do or even reading the new manual.  Pretty much the same unimpressive tome that should really be of interest only to psychiatrists and then briefly.  There are more exciting things to read about psychiatry.

Fake psychiatric news is some of the most abundant fake news in medicine.  It is a prime example of the types of fake news that exists out there and what some of the motivations are.  The number one read post of all time on this blog focuses on a Washington Post article, basically correcting what was said about the DSM-5, conflict of interest, primary care, and psychiatry.  Should that level of correction render it into the fake news category?  The fake news in psychiatry is so pervasive there are entire web sites dedicated to it.  Some of these web sites have an air of legitimacy until you read what is actually being said.  Some even attract psychiatrists who are apparently confused about the content or tenor of the site and don't seem to understand rhetoric.

Just a few things to consider about the current fake news category - especially as it applies to psychiatry.  Fake news is here to stay - it is not some new problem introduced by Google or Facebook.  It is all a part of how society works, with a person or group of people seeking advantages over others.  In the USA we like to fool ourselves into thinking that we live in a fair society where everyone is equal.  We like to think that conflict-of-interest can be eliminated or at least managed.

That is just more fake news.

George Dawson, MD, DFAPA


1:  Cathy O'Neil.  Social Media Companies Like Facebook Need To Hire Human Editors.  NYTimes Nov. 22, 2016

2:  New York Times Opinion Pages:  How To Stop The Spread of Fake News.  NYTimes Nov. 22. 2016.

3:  Ioannidis JP. Why most published research findings are false. PLoS Med. 2005 Aug;2(8):e124. PubMed PMID: 16060722.

4: Ioannidis JP. The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-analyses. Milbank Q. 2016 Sep;94(3):485-514. doi: 10.1111/1468-0009.12210. PubMed PMID: 27620683.

Ioannidis concludes that despite the massive production of meta-analyses only 3% are "decent and clinically useful."


Saturday, November 19, 2016

An Unstated Developmental Milestone (or Two)

It is hockey season in Minnesota.

And like Little League seasons used to be, tens of thousands of pint sized hockey players are competing and practicing almost on a 24/7 basis.  Emotions run high as teams of widely varying levels of physical ability compete for the greater glory of their team.  Like most team sports that we all played as kids, there is a high emotional investment in winning.  None of the secondary goals of personal improvement, improved conditioning, and teamwork are generally considered.  Whether or not they can be realistically considered at a young age is an open question.  Clearly the adults carting all of these kids around and in many cases coaching them - want to see them win.  I don't know what impact the participation movement has had on winning.  In talking with some graduates of those systems, it offers limited protection.  At some point there is only competitive sports and a rude awakening that participation gets you so far.  At some point everybody does not get a trophy.

That realization is a game changing event for most people.  In your high school class of 300 people, you might be the fastest person in the quarter mile but you rapidly learn through a series of track meets that you will probably not be going to the Olympics.  The adaptation to that varies from just quitting the track team, to going to all of the meets and running as fast as you can, to questioning the coaching staff,  to trying performance enhancing drugs to see if that will give you the necessary edge.  It involves more than sports.  I have seen the same sequence of events play out in music and academics.  Being demoted from second to third chair in the orchestra section.  Not getting the perfect score or academic award in school.  In relationships, the break up of a first serious romantic relationship was the commonest reason I would see college aged students admitted to my inpatient unit and yet - none of them had a serious mental illness.  They were "suicidal" and emotionally distraught because they had not dealt with that kind of failure before.  My standard pep talk to them was that someday they would be as old and emotionally resilient as me and they would have scant recollection of ever seeing a psychiatrist in their life.  In many ways, relationships more than anything else highlights the developmental milestone I am referring to and that is dealing with failure - especially when that failure seems to have very high stakes.  A large percentage of the college students in crisis did not think that they would ever find a partner as ideal as the one they had just lost.

In Psychiatry School, they teach us all the normative models of cognitive and emotional development from various schools of thought.  Reading any modern text of child psychiatry (1) - the old developmental references based on theories by Freud, Piaget, and Erickson are gone.  They are now supplanted by specific emotion, cognitive, temperament, and attachment lines of development and their associated neurobiology. It is generally agreed that it is better to be resilient than not.  We now know that psychological trauma in childhood is a major cause of decreased resilience and that a fair number of children experience one of these traumatic events during childhood.   Apart from protecting children from these traumas as parents and society - what else can be done on an individual level?  During my career as a psychiatrist, I have made two observations that originated with other people that I think would be extremely helpful.

The first is the Sara Blakely story.  She is  the CEO of Spanx, a company that she started herself that became amazingly successful.  She has told her story repeatedly on a method that her father taught her to redefine failure as not trying rather than the outcome.  Her father took an active interest in his children and always inquired aboiut one thing they had failed at that week.  She said that he actually celebrated their failures at some point.  She discloses her failures at her company and encourages her employees to do the same thing.  Having survived several corporate cultures that thrived on blaming employees for various problems, I can imagine (if I try real hard) how refreshing that approach would be.  What would happen to all of these kids playing Minnesota hockey if they were able to just talk about what they were trying to do and how they failed at it?  Would it revolutionize the game?  If you are focused only on a win-lose outcome, you lose a lot of information along the way.  Information about yourself  and everybody else.  The starkest piece of information is that at any level of competition, the odds are stacked against you being the big winner.  You have to be able to see yourself as the Big Fish in a small pond at best.  You are probably not the one person in a million who is going to be at the top of that game.  In my estimation Sara Blakely's father was a genius when it comes to parenting.

I learned about the second genius father from of my coworkers before one of my morning inpatient team meetings.  We were the first ones there and she started talking about how she got into nursing.  Her father advised her to do volunteer work in the field when she was in high school.  She was reluctant to consider that idea.  At that point her father said her would pay her to do volunteer work in a field that would help her get into the health care professions.  At the time that struck me as pure genius.  I was talking with an extremely competent nurse.  I could also relate to not wanting to do much and not realizing why volunteer work as a teenager might be important.  That single idea by her father may have been the difference in her vocational choices.        

Those are my two favorite stories about parenting ideas that seemed like pure genius to me.  I am very interested in hearing what other people have discovered in real life that might have been useful in  improving resilience and getting to a more useful perspective on life - as opposed to the dry theories that we are all taught.  I would also like to point out that these issues are very difficult to study in a double blind clinincal trial, but I did encounter an experiment that was applied to a school class that also had very good results.  The study was highlighted by Ruth Shim, MD, MPH in her presentation Prevention in Psychiatry: A Public Health Approach given at the the University of Wisconsin 4th Annual Update in Psychiatry this year.  The research presented was on the Good Behavior Game (GBG), an intervention applied in the Baltimore City Public Schools in the late 1960s.  The game starts as three 10 minute sessions per week as a team competition.  The rules were focused on working quietly, being polite to others, getting out of one's seat with permission, and following directions.  Teams were rewarded with pencils and erasers if all of the members of the team followed the rules.  As the game went on the sessions got longer and students were given stars as rewards.  The games started with 1st and 2nd grade students and continued until the 6th grade.  Students were assessed up to the age of 19-20.  When the GBG classrooms were compared to standard classrooms there were significant reductions in alcohol use, smoking, and suicidal thoughts.  Looking at the males only there was less substance use and need for behavioral and substance abuse treatments.  The highly aggressive male strata had substantially less drug abuse, violent and criminal behavior (34% versus 50%), and diagnoses of adult antisocial personality disorder ( 40% versus 100%).

All of those results from the straightforward application of behavior therapy and peer pressure.  These are all good examples of basic ideas that seem to have had very good outcomes in terms of competent and successful adults.

George Dawson, MD, DFAPA


1:  Anita Tharper, Daniel S. Pine, James F. Leckman, Stephen Scott, Margaret J. Snowling, Eric Taylor.  Rutter's Child and Adolescent Psychiatry (6th ed).  John Wiley & Sons, Ltd, The Atrium, Sounhtern Gate, Chichester, West Sussex, UK, 2015.  

2:  Embry DD. The Good Behavior Game: a best practice candidate as a universalbehavioral vaccine. Clin Child Fam Psychol Rev. 2002 Dec;5(4):273-97. Review. PubMed PMID: 12495270.


Hockey photo at the top is by y Ailura (Own work) [CC BY-SA 3.0 at (], via Wikimedia Commons at the following URL:

The Surgeon General's Report on Addiction

Last week, the current Surgeon General Vivek H. Murthy, MD came out with the first report from that office on addiction.  The full text is available on line at this link.  The document is 428 pages long but it is full of a lot of unnecessary text.  As an example the first 64 pages are essentially an introduction and a listing of personnel who worked on the report as well as references.  The last 85 pages are references and appendices.  I don't know the chain of command but both the US Department of Health and Human Services (DHHS) and the Substance Abuse and Mental Health Services Administration (SAMHSA) have their imprint on it and that is not necessarily a good thing.  The Surgeon General came out with a letter earlier this fall about how to stop the opioid epidemic that I commented on.  That letter was brief, to the point, and could have been expanded into a more concise document than the current report.

There is a lot wrong with this report.  Just from an administrative side, it is clear that the report sends a strong public relations message about what the government is doing to advance the treatment of addiction and a lot of that message is flat out spin.  I am always interested in detoxification from addictive drugs so I naturally searched on that and found this paragraph:

 "Until quite recently, substance misuse problems and substance use disorders were viewed as social problems, best managed at the individual and family levels, and sometimes through the existing social infrastructure—such as schools and places of worship, and, when necessary, through civil and criminal justice interventions. In the 1970s, when rates of substance misuse increased, including by college students and Vietnam War veterans, most families and traditional social services were not prepared to handle this problem. Despite a compelling national need for treatment, the existing health care system was neither trained to care for nor especially eager to accept patients with substance use disorders." (p 1-19).

That is really not what happened.  It is not even close.  Services to treat addiction were rationed just like services to treat mental illnesses.  With the federal and state governments giving carte blanche to managed care companies - hospitalizations that required detoxification could be denied even if the patient had a significant psychiatric disorder.  Trauma surgeons were also affected by this discrimination.  People with serious traumatic injuries who also had positive toxicology for drugs or alcohol were denied payment for a hospitalization that required extensive surgery and prolonged hospital stays.  The very thin system of care for addictions and mental illness were outside of the funding stream of mainstream medicine because that is exactly where the government and the business world placed it.  In the entire document there is one reference to prior-authorization (p. 6-24) and then only to say that it is one of many strategies used by states to ration Medicaid resources used for treating addictions.

On the issue of training, in about 1992 I had accumulated a series of cases that involved inpatient detoxification that were denied payment by a managed care intermediary representing the state government.  All of these denials have appeal processes that are stacked against physicians and patients.  In this case I was told I would need to argue all of them in front of an administrative law judge.  I took a vacation day and was ready to do that.  On the day before the hearing, I was notified that the judge had made a summary decision in favor of the managed care company and I did not have to show up for the hearing.  This is obviously not a training issue when I am doing detoxification, a managed care company is telling me to discharge patients (2/3 of whom also have significant mental illnesses), and the state is backing them up.

In the entire document there are 4 paragraphs on detoxification - referred to as "Acute Stabilization and Withdrawal Management". (p. 4-12 - 4-13).  It really minimizes the medical aspects of detoxification and the potential complexity of the situation to the degree that it seems to have been written by a nonphysician.  The clear intent is to stress that detoxification by itself is not treatment for an addiction but only a necessary first step.  In the process it also minimizes the medical and nursing expertise necessary to get people through the detoxification phase.  After an entire chapter on neurobiology there is no mention of the craving and dysphoria that often prevent people from completing detoxification or cause them to immediately relapse afterwards.  There is no mention of the medical comorbidity that needs to be addressed along with the detoxification process.  There is no mention of the complexity involved in detoxifying people from multiple addictive substances - a common scenario these days.  There is no mention of why allowing people to detoxify themselves at home with addictive substances may or may not be a good idea.  There is no mention of why "social detoxification" in non-medical detox centers run by municipalities may or may not be a good idea.  There is no mention of the psychological aspects of detoxification and why it presents one of the most significant obstacles to care in the treatment of addiction.  In short, detoxification would seem to have a much more prominent role in a report about facing addiction than it does in this report.  The treatment of addiction would have been better served if all of these issues would have been addressed and the minimum medical requirements for detoxification could have been established.  

On the less wrong but not perfect side of things, there is a lot of neurobiology in the report, both in terms of basic science and medication assisted treatment.  The neurobiology is fairly intense for the average reader who is part of the target audience.  Even at the level of physicians who I lecture to and train the concept of the extended amygdala is comprehended by very few people.  I could probably say the same thing about the amygdala.  In fact, I attended a course of brain dissection by one of the pioneers of this concept Lennart Heimer, MD.  At the end of that two day course, in a room of highly motivated and interested people I think that few understood the importance of the concept.  My point in all of this is the old adage - you can know just enough neurobiology to be dangerous.  At some point all of these names just become pseudo-explanations, especially for people with a poor understanding of science.  I have talked with people who knew all of the jargon and started to explain their own addictions with it.  That was not a good scientific or clinical approach and I wonder if the public may have been better served by an approach that focuses on the conscious state of the addict.  We still do not know how that is derived from the underlying neurobiology - even though the neurobiological explanations make it seem like we do.  

Criticism aside, there are some things that the report does well.  It provides a fair outline of the NIDA based continuum of care guidelines for addiction treatment for people with severe addictions.  The specific section can be found starting on  page 4-13 and the section: Principles of Effective Treatment And Treatment Planning.  The average person or family interested in seeking treatment for someone with an addiction is often faced with a staggering array of treatment services and a lot of associated politics.  The news media is often a source of increasing confusion rather than clarity.  A recent example is the rise of certain treatment methods that claim very high rates of success, or that are critical of more traditional treatment approaches like 12-step recovery (AA, NA, TSF (Twelve-Step Facilitation Therapy) and residential treatment.  Managed care companies continue to ration residential treatment 1 or 2 or 5 or 7 days at a time.  From the report:

"A typical progression for someone who has a severe substance use disorder might start with 3 to 7 days in a medically managed withdrawal program, followed by a 1- to 3-month period of intensive rehabilitative care in a residential treatment program, followed by continuing care, first in an intensive outpatient program (2 to 5 days per week for a few months) and later in a traditional outpatient program that meets 1 to 2 times per month. For many patients whose current living situations are not conducive to recovery, outpatient services should be provided in conjunction with recovery-supportive housing."  (p. 4-18).

That recommendation on the continuum of care should be kept in mind by anyone who is seeing an addiction specialist from any discipline in their office on an outpatient basis and finds that they are not able to stop using drugs or alcohol.  That would include physicians or other prescribers who are providing medications and possibly making the situation more dangerous because of the combination of prescribed and addictive drugs.  There is a temptation to say that with new innovations in medication assisted treatments that all that is necessary is seeing a physician and getting medications to treat the addiction.  A close read of any of the FDA approved package inserts on these medications addresses the complexity and points out that psychosocial treatments like the ones in the above paragraph are necessary.  There is no strictly medical cure for addiction.

It is also fairly common these days to see Alcoholics Anonymous and their principles being bashed in various forums like the popular media or web sites that seek to aggregate professionals.  They appeal to people who don't like the model for various reasons, consider it antiquated, or claim more success using some other treatment.  Some of these sources are also confused, often by neurobiology or an ignorance of the treatment literature and claim that there is no evidence that 12-step recovery works.  The report provides solid evidence to the contrary.  TSF is listed as a treatment intervention with a solid evidence basis and results as good as any and it works as a stand-alone intervention or in combination with other treatment modalities (p. 4-28 to 4-30) that are often suggested as competing treatment models.

That's my overall take on the report.  Like most government documents it is a lot of unnecessary reading so I may have missed something and I can't comment on everything.  It is clearly the product of committees, meetings, and bureaucrats.  Documents like these serve a variety of purposes in addition to the stated purposes of educating the public and establishing public health policy.  As a person who lived through it, this is also a serious rewrite of history.  That history is decades of what has been called "health care reform".  In this country that means hiring proxies to ration healthcare.  When that happens the most disenfranchised patients get the most rationing.  Those patients have always been people with addictions and mental illnesses.   The real intervention needed in the addiction treatment landscape is establishing some controls on companies who are set to profit from denying care for addiction treatment and the governments that encourage it.

That is the single-most powerful intervention that we need in the addiction treatment field and it was nowhere in the report.

George Dawson, MD, DFAPA


U.S. Department of Health and Human Services (HHS), Office of the Surgeon General, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS, November 2016.


I have no connection with any of the parties of agencies who wrote this report.  I am obviously a psychiatrist with a life long commitment to treating mental illness and addiction and extensive personal experience with the rationing of these treatment services.  I am currently employed at a treatment center that uses most of the treatment modalities specified in this report including medication assisted therapies (MAT).

Friday, November 18, 2016


There is an outstanding review of pancreatitis in this week's New England Journal of Medicine.  I thought I would add it here as a reference for any addiction or medical psychiatrists who come across this post and may not be regular readers of the NEJM.  I recommend getting the entire article because it has an excellent table and infographic.  The table is on the causes of acute pancreatitis.  The top two - gallstones (40%) and alcohol (30%) have not changed since I was in medical school.  Hypertriglyceridemia (defined as fasting triglycerides >1000 mg/dl) was the third most common cause at about 2-5% or the total.  Some of the causes occur only in a very specific context like endoscopic retrograde cholangiopancreatography (ERCP) and patients undergoing cardiopulmonary bypass.  In both cases, the authors estimated that 5 -10% of patients undergoing these procedures got pancreatitis.  Although the ERCP was expected I was surprised that many cardiopulmonary bypass patients got pancreatitis.  The remaining 5-8% are caused by medications, viral and parasitic infection, and blunt trauma.  Psychiatrists should be aware of valproic acid/valproate correlation with pancreatitis,  especially if they are treating patients with significant alcohol exposure.  Some facilities use a valproate detox protocol and those patients need to be carefully assessed for alcoholic liver diseases and undiagnosed pancreatitis.

The diagnostic features of acute pancreatitis are reviewed and these are important for any acute care psychiatrist who is seeing patient with associated risk factors.  At the clinical level abdominal pain and elevations of amylase and lipase 3 times the upper limit of normal are the initial features that require confirmation by MRI or CT imaging finding consistent with the disease.  From a diagnostic perspective the availability of testing and practicing in a medical facility are limiting factors.  Any abdominal pain with a suspicion of pancreatitis in a non-medical facility makes a trip to the emergency department for rapid assessment and diagnosis most reasonable.

The infographic was on the time course and management of acute pancreatitis.  The time frame used was 6 weeks.  80% of patients with acute pancreatitis have self limited disease and are discharged from the hospital in a few days.  The incidence of acute pancreatitis is rising with a 20% increase in admissions in the past decade.   On the mortality dimension half of the deaths occurred in the first two weeks due to multiple organ system failure.  The other other half of the death occur after two weeks and are due to pancreatic and extrapancreatic infections.  On the pathophysiology dimension, 80-85% of the disease was the interstitial form and 10-15% the necrotizing form.  There was also a therapy dimension outlining critical markers such as aggressive fluid resuscitation in the first 24 hours and enteral nutrition after day 5 if tolerated.   The therapy dimension was linked to the text that reviewed state of the art details on the medical and surgical management of the disorder.  These sections will not apply to psychiatrists, but the authors point out common mistakes in management including the unnecessary use of total parental nutrition and antibiotics for presumed pancreatic infection.   The main lessons for psychiatrists at that stage is that patient management has exceeded the capabilities of psychiatric settings and that the patient must be transferred as soon as possible to an appropriate medical setting.  Once that has occurred, the plan to take the patient back when stable also requires a clear plan with the attending who is discharging the patient.

The other highlights in this article from a psychiatrist's perspective was the estimated dose of alcohol necessary to cause pancreatitis.  The authors give that as 4 - 5 drinks per day for 5 or more years.  This is well below the dose of alcohol required for cirrhosis and probably explains why larger numbers of young patients are seen with pancreatitis.  Apparently, in the 2-5% of heavy drinkers that develop pancreatitis it occurs as a chronic form initially with episodic acute exacerbations superimposed on this chronic form.  That also explains why binge drinking does not precipitate acute pancreatitis.  Diabetes, smoking, and obesity are seen as correlates of acute pancreatitis but not direct causes and these are all significant comorbidities in patients with psychiatric disorders.  Once an episode of pancreatitis has occurred abstinence from alcohol is critical because it decreases the likelihood of recurrence.  The authors reference a structured consistent intervention that they cite as being successful (2).  I don't have access to the full text of this article, but it suggests that an infrequent intervention by a nurse in outpatient clinic is more effective than a single intervention during  hospitalization in preventing relapses.

This was a great overview of acute pancreatitis by some of the top experts in the field.  It is another problem that you never want to miss.  It is a reason to resist simplifying biochemical screening of patients on admission or clinic intake.  Since metabolic syndrome, obesity, and tobacco use is high and elevated triglycerides may be a factors in the pathophysiology of pancreatitis - it seems reasonable to do metabolic screening on patients without recent testing.  If you are seeing patient with risk factors particularly alcohol use, tobacco use, obesity, and diabetes - discussion of lifestyle management, smoking cessation, and abstinence from alcohol is useful in addition to the discussion about their primary psychiatric problem.  Addiction psychiatrists will probably see significant numbers of patients with chronic pancreatitis and a discussion with them on how to prevent recurrences and their understanding of the illness is important.

George Dawson, MD, DFAPA


1. Forsmark CE, Vege SS, Wilcox CM. Acute Pancreatitis. N Engl J Med 2016; 375: 1972-1981.

2.  Nordback I, Pelli H, Lappalainen-Lehto R, Järvinen S, Räty S, Sand J. The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial. Gastroenterology. 2009 Mar;136(3):848-55. doi:10.1053/j.gastro.2008.11.044. PubMed PMID: 19162029.


Monday, November 14, 2016

The Harvard Neuropsychiatry Course

I went to the Harvard Neuropsychiatry course for all of the wrong reasons.  I started going to HMS courses in Boston back in the late 1980s.  I have always seen myself as a medical psychiatrist knowledgeable in neurology, medical imaging and electroencephalography.  I have always liked seeing people with complicated problems that are associated with psychiatric diagnoses or who have psychiatric symptoms associated with their primary medical or neurological diagnoses.  That led me to the Behavioral Neurology courses through Harvard where the presentations were done by all of the experts at time including M-Marcel Mesulaum, Antonio Damasio, Hanna Damasio, Elliot Ross, and David Bear.  Their work is well represented in the text Principles of Behavioral and Cognitive Neurology.  At the time there were some older neuropsychiatry texts but learning about the field generally had to occur on a reference by reference basis.  I was working in a Memory Disorders and Geriatric Psychiatry Clinic and learning neuropsychiatry on a syndrome by syndrome basis.  I did not find out until this course that it is the largest meeting in the field and has been occurring on an annual basis for the past two years.  My motivation for coming was basically to see whether I missed anything.  I always need to answer the question: "Can a clinician working too many hours per week keep up with a technical field to an acceptable degree."  For the first time ever in my career I was spending a lot of money on a conference and travelling well outside my comfort zone to see presenters who I did not know that well.

There were about 320 people registered for the course.  The setting was a hotel built in the early 20th century but extensively remodeled to 4 star hotel status.  The conference itself took place in the main ballroom and it was densely populated with some overflow into balcony seats and a mezzanine area in the back.  The audiovisual effects worked with with a large projection screen over the speaker and large LEDs TVs lining each side of the ballroom.

The  overall format of the course was to present a lot of technical information on Day 1 and discuss more discrete diseases and syndromes on Day 2.  The detailed agenda for both days can be found at this link.  Day 1 was a focus on neuroanatomy, functional brain networks, neuroimaging,  neuropsychiatric and neuropsychological approaches to the complex patient, and a detailed approach to the complex patient.  These were not TED talks.  The first three presentations covered 81, 60, and 60 slides.  That is the way I like it.  An additional benefit is that all of the PowerPoints were available in PDF form online.  Even the most unreadable slides are easily visible in this form.  The PDF form is also allows the syllabus to be printed in black and white and used primarily for note taking.  Legibility of the slides depend on the print size and many in this syllabus were unreadable.  I think that all conferences should use this approach.  I would like it modified so that the original slides could be reused in lectures by Creative Commons licenses.

The early lecturers used a lot of subordinate clauses and very long sentences.  I could imagine that anyone unfamiliar with the jargon could get lost.  The lecturers were unapologetic and one of them suggested studying the slides and references to get up to speed.  The pace of the course was intense with brief coffee and lunch breaks in order to cover the advertised CME.  Several of the lecturers ended up accelerating their presentations as they realized that they were running out of time.  My focus in these conferences is on information transfer and not style points on the lectures.  At that level I consider it a success.  Key points were highlighted as well as references.  There were a couple of graphics that were not referenced.  The syllabus for the course is 453 pages long and could easily be worked into a text at some point.

In the past, I have reviewed all of the lectures at conferences.  For this conference I am going to mention a couple of high points.  There is some confusion about what neuropsychiatry is.  Barry Fogel, MD defined it at the end of Day 1: "Neuropsychiatry is a branch of clinical neuroscience more than a mental health discipline.  It is always in the context of the brain."  Every lecturer maintained that theme reviewing key brain circuits involved in pathological states including some that were considered to be functional as well as states associated with clear brain pathology.  In some cases those formulations were associated with a new conceptualization of the disorder.  A good example, is the case of traumatic brain injuries (TBI).  Tom McAllister, MD made the point that not too long ago, nobody would have showed up for a lecture on TBI.  Those were the days when it was common to consider TBIs, especially occurring in sports to be minor events.  That has been reconceptualized from the perspective of neuropathological changes, protein markers (Tau, APP, Aβ, and others), and possible progression to dementia.  The treatment of neuropsychiatric syndromes of TBI including depression, PTSD, and other psychiatric syndromes.  I am used to seeing a lot of people with bipolar like syndromes after TBIs but that was not mentioned.  Excellent reconstructions of the brain with a map of the results of a large number of TBIs were presented with an emphasis on the circuitry affected and how that can lead to symptoms.

When I think about earth shaking information on a single slide (yes - it can happen) - the best example I can think of was a slide in the presentation: Neuropsychiatric Aspects of Frontotemporal Dementia by Brad Dickerson, MD.  For anyone who has followed it, the diagnostic approaches to this relatively common dementia have been confusing over the years (2).  In a slide FTLD (Frontotemporal lobar degeneration) clinicopathological spectrum parses the 6 major clinical  syndromes into subtypes based on biological markers.  Each category was also color coded to indicate the degree of tauopathy.  I found a modified version of this slide in an article by Irwin, et al in Frontiers in Aging Neuroscience (1).  These same authors have published a significant number of the papers in the field.  This review stood out to me because it is the clearest conceptualization of FTLD that I have seen.

The second high point of the conference was on Functional Neurological Symptom Disorder (FNSD).  This is actually a subheading under Conversion Disorder in the DSM-5 (p. 318) and the main diagnosis is the disorder known to most psychiatrists.  The disorder is one of pseudoneurological symptoms like weakness, paralysis, sensory symptoms, speech problems, or seizures with no known correlates of the medical diagnosis.  The presentation by Gaston Baslet, MD on the approach to these disorders was very informative.  Rather than take a strict DSM criteria approach, he presented the criteria and then illustrated levels of diagnostic certainty - the levels of diagnostic information that are ideal versus what is clinically available.  The example given was for Psychogenic Non-Epileptic Seizures (PNES).  The increased prevalence of these disorders in neurological practice as opposed to primary care was noted.  Most importantly, the approach to treating the disorder was discussed as well as what seems to work.  A model of predisposing, precipitating, and perpetuating factors was presented.  Like most disorders, cognitive behavioral therapy (CBT) is a useful treatment modality either as psychotherapy delivered in a  standard approach or using a self help manual.  Dr. Baslet also discussed a communication protocol on how to present the diagnosis and rationale for treatment to the patient.  Limiting factors include the low number of patients who complete treatment and there is a spontaneous improvement rate of about 20%.  A neurobiological model of PNES/FNSD was presented based on the work of van der Kruijs, et al (3).  This is important work for any psychiatrist who has not had the experience of treating PNES/FNSD on an ongoing basis with psychotherapy.  My experience is consistent with the presentation in that it takes good communication with the patient and an effective model for therapy to get results.

Forced normalization epilepsy was a term that I was unfamiliar with even though I have treated a significant number of people with seizure disorders.  It was discussed in Gaston Baslet's second presentation on the Neuropsychiatry of Epilepsy.  It is a description of a syndrome where psychotic states occur as the EEG abnormalities of the seizure disorder improve or disappear.  The neuropsychiatric symptoms that emergence when this occurs is also referred to as alternate psychosis.  There is a small but significant literature on this problem that also highlights some of the controversies.  His presentation also discussed the safety of antidepressants in epilepsy and the FDA warning on suicidality and antiepileptic drugs (AEDs).  Since I prescribed a lot of gabapentin in the treatment of addiction, anxiety, and chronic pain - that is a warning that I have to address a lot with patients.  He showed the Forest plot of odds ratios for specific AEDs and according to that reference (4) some drugs may be protective for suicidal ideation and behavior.  With the discussion of emerging and interictal psychotic symptoms an equivalent brief discussion of antipsychotic drugs in these states would also have been very useful.  Dr. Baslet also mentioned one of my favorite neuropsychiatric symptoms Alice In Wonderland Syndrome or metamorphopsia as it is sometimes known.  Like Alice, patient's experience body distortion (feeling too tall, floating, sinking into the ground) as a manifestation of infectious disease (originally Epstein Barr Virus), migraines, or epilepsy.

A  final brief point was noted in the presentation on neuropsychology by Aaron Nelson, PhD.  It is useful at a time when I think there is a lot of controversy about these assessments and what they show.  The commonest reason I see patients getting a neuropsychological assessment these days is Attention Deficit-Hyperactivity Disorder.  It is generally presented to me as proof of the disorder and proof that a person needs stimulant medications.  The patient generally reports that they were "tested" for ADHD and found to have it despite a normal development history, normal and typically good academic performance, and good vocational achievement.  I have previously posted that Russell Barkley, PhD one of the leading authorities on ADHD has stated that neuropsychological testing is neither necessary or sufficient to make a diagnosis of ADHD and as it is based on clinical criteria.  Of course the main reason for neuropsychological testing of individuals suspected of having ADHD is to test for any associated learning disorders and in the adult patients I see - very few people recall any information of that sort.  Dr. Nelson points out that intraindividual variation in neuropsychological test performance is common with 66% or participants in his study (6) producing maximal discrepancies that exceeded 3 standard deviations on test performance.  His conclusion is that score variability alone is not enough to base diagnostic inferences on.  Dr. Nelson also called for a show of hands to see if any clinicians had access to neuropsychological testing in a time frame of less than 3 months.  There were few if any hands raised.            

Those were a few of my favorite highlights from this conference.  There are many more, but I am trying to keep this post contained to the highlights and overall focus.  This is an intense conference but a good one.  In the follow up assessment, they asked if the course should be three days rather than two and I endorsed that approach.  I think that the inflammatory section of neuropsychiatric disorders could be reinforced by having any of the psychiatrists who write the sections in Lahita's text on Systemic Lupus Erythematosus present on that topic. If your priorities in conferences are similar to mine (information transfer, non-experiential, and a direct comparison of your skills to the experts are a priority) - you might want to attend this conference next year.  The course organizers did have question and answer sessions regularly throughout the program and questions were actively solicited by course staff and read and answered by the lecturers.

And it turns out my approach to self-study has paid off.  There were several points where I could have stood up and given the lecture.  That may seem immodest if you believe that practicing psychiatrists need to be constantly tested and reassessed by some higher authority to prove that they are competent.   I don't and never have.  It turns out all you have to do is practice medicine, think a lot about what you are doing and try to keep up on the literature.  At one point the lecturers asked about how many people in the audience were psychiatrists and then how many have treated people with frontotemporal dementia.  Most of the people were psychiatrists and most of them have assessed and treated frontotemporal dementia, despite the fact that the diagnostic classification has been in a state of flux for the past 20 years.  Thinking about that, there was a tremendous amount of knowledge about neuropsychiatric disorders in that room.  I can't imagine that this disorder or the general importance cerebral atrophy on imaging  is well recognized in primary care settings.  That is just one of the reasons why neuropsychiatrists are needed out there and why these concepts need to be taught and understood in residency training.

George Dawson, MD, DFAPA


1:  Irwin DJ, Trojanowski JQ, Grossman M. Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer's disease. Front Aging Neurosci. 2013 Feb 21;5:6. doi: 10.3389/fnagi.2013.00006. PubMed PMID: 23440936; PubMed Central PMCID: PMC3578350.

2:  Kertesz A, Munoz DG.  Frontotemporal Dementia; in:  Alzheimer Disease. RD Torrey, R Katzman, KL Bick, SS Sisodia (eds); Lippincott Williams and Wilkins; New York; 1999; pp 133-145.

3:  van der Kruijs SJ, Bodde NM, Vaessen MJ, Lazeron RH, Vonck K, Boon P, HofmanPA, Backes WH, Aldenkamp AP, Jansen JF. Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):239-47. doi: 10.1136/jnnp-2011-300776. PubMed PMID: 22056967.   JNNP has a collection of Neuropsychiatry articles up until 2015.

4:  Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepilepticdrugs: Fire or false alarm? Epilepsia. 2009 May;50(5):978-86. doi: 10.1111/j.1528-1167.2009.02012.x. Review. PubMed PMID: 19496806.

5: Hesdorffer DC, Berg AT, Kanner AM. An update on antiepileptic drugs andsuicide: are there definitive answers yet? Epilepsy Curr. 2010 Nov;10(6):137-45. doi: 10.1111/j.1535-7511.2010.01382.x. PubMed PMID: 21157540.   

6: Schretlen DJ, Munro CA, Anthony JC, Pearlson GD. Examining the range of normal intraindividual variability in neuropsychological test performance. J Int Neuropsychol Soc. 2003 Sep;9(6):864-70. PubMed PMID: 14632245.


The graphic at the top of this post is the cover of my syllabus for this course.  I have no affiliation with the course or Harvard Medical School, I just paid the fee to take the course like everybody else.  The graphic is included here is to provide information about the course that I reviewed in this post.

Wednesday, November 9, 2016

Personally Intervening in the Case of Public Intoxication

I am at the Fairmont Copley Plaza Hotel in Boston.  I made the trip for the Harvard Neuropsychiatry Course.  My wife and I decided to go out and look at some architecture and walked out the side entrance onto Dartmouth Street.  There on the sidewalk was a young woman who appeared to be doing a down dog.  The only problem is that she did not seem to be able to get out of it.  As she pushed herself up, it was apparent she was severely intoxicated.  She had drawn a small group of observers, people were staring at her and not doing much of anything.  Being strangers in town we decided to keep moving and let the locals handle it and headed down Dartmouth toward Boylston Street.  After about 100 yards the young woman got up and started walking down the sidewalk and at times staggering into the street.  Vehicles travelling at about 30-40 mph had to stop or take evasive action in order to avoid her.  She was not aware of the near misses and kept wandering farther out into traffic.  This was unfolding in full view of hundreds of people in Copley Square and three television camera trucks interviewing people about the election results.

At that point, I could not stand by to wait for her to get hit by a car.  I was in Philadelphia once back in 1975 on a packed sidewalk.  At the red light a guy next to me inexplicably stepped off the curb against the light and was hit by a speeding van.  I can still see his body arcing through the air and landing face down on the asphalt about 50 yards away. I don't want to see that again.  I walked up to the woman and physically guided her back onto the sidewalk and asked if I could call someone.  She was obviously intoxicated and her speech was 80% unintelligible.  She was able to tell me that she wanted to get on a subway train to a suburb.  There were two subway stations available and a passerby helped us out by telling us where we needed to take her.  I helped her across Dartmouth and at that point she became agitated and started to walk out into the street again.  I tried to guide her to a seat at a bus stop and she slumped against the edge of the bus shelter and it looked like she was going to fall asleep.  At that point, I asked my wife to call 911, because it was obvious that she could not safely travel on her own.

She became agitated and angry.  She demanded to know where I was taking her and bolted across the street to the the wrong subway station.  We had the 911 operator on the line and when we reported what happened, the operator said: "well she's on the subway - it's out of our hands now" and hung up!  We crossed the street and went underground looking for her.  I was concerned that she would fall off the subway platform.  She had negotiated the turnstiles and it was not obvious how that happened, but there were some embarrassed looks on the faces of the transit personnel.

I watched her get on the train.  One precarious short step forward, followed by a long lean backwards.  During the lean, all of the exiting passengers halted in their tracks as if they were waiting for her to fall over.  After a few seconds - she regained her balance and plummeted past them onto the train.  The train pulled out and she was gone....

We helped her as much as we could.  Two people assisted us, hundreds did not.  We avoided a catastrophe - at least in our immediate vicinity.  From the public official we called, that was apparently all that the citizenry of Boston expected.  I did not notice until later at night that there were a significant number of people with chronic mental illness around Copley Square.  Many of them were incoherent or shouting illogical statements in a loud and vaguely threatening manner.  Still - they were not wandering in traffic and appearing to be at high risk for a fatal encounter.  It is possible I guess that the threshold for intervention is altered in that context, but the young women in question was neatly dressed and obviously ataxic, dysarthric, and sedated at times. In that case, the many people who saw her decided to do nothing but watch.

I thought I would document this all here with a suggestion.  If you see a fellow citizen intoxicated and in danger, I recommend intervening in that situation.  I don't think that you want to be second guessing yourself if you elect to do nothing and witness a catastrophic event.  This is a clear example about why public intoxication is not a humorous event like it is typically portrayed in the movies. It is also an example of the limits of what can be done.  Of course you always have to use your judgment in these situations.  You  can't put yourself in danger.  Private citizens cannot take physical custody of another person.  I could only help this person as much as she would allow even though her judgment was clearly impaired.

Acute intoxication can easily be a life threatening experience.  The danger can be either the direct result of the intoxicant or the result of inadequate self care.  I have seen too many people killed outright or in a trauma or burn unit because of that lack of ability to take care of oneself.  Even an unsupervised fall at home can be fatal.

So - do what you can.......

George Dawson, MD, DFAPA      


For some reason, I have had the opportunity to intervene in many of these incidents in the past varying from a retiree backpedaling out of a rural convenience store and slamming into me at 7AM in northern Wisconsin - to picking up someone off a hospital floor and getting him to the Emergency Department.  My wife was with me for the first incident and she was quite upset thinking that the old guy had a heart attack or a stroke.  I told her not to worry - he was drunk even though it was 7 AM and he had driven himself to the store across a busy highway.


Photo at the top is from Wikimedia Commons with the following references from that site: By User:Eos12 (Own work) [Public domain], via Wikimedia Commons per the listed release into the public domain by the originator.


Tuesday, November 8, 2016

Foreign Policy Implications Of The Business Takeover Of Medicine

Don't worry.

This post is not about the current Presidential election.  I have no horse in the race.  Nobody to vote for.  I have been a staunch 3rd party voter for a long time and there is not even a third party candidate that I would currently vote for.  I know that opens me up to criticism from major party partisans who commonly accuse independents of either losing them the election or being too arrogant to hold their nose and vote like everybody else.  I trust my nose more that I trust that kind of rhetoric.  The current campaign highlighted everything that is wrong with the political process including a lack of focus on real issues, a lack of inspiring candidates,  and plenty of dishonesty on both sides.  I want to focus on one real issue and that is national security.  And I want to get at it from a perspective that is described primarily on this blog.

Early in the 21st century, I involved myself in a lot of political debates.  As an example, I was very active in the debates about whether the United States should have invaded Iraq under President George W. Bush.  At the time there was the unfounded belief that Iraq had weapons of mass destruction and a push to invade even though UN weapons inspectors under Hans Blix had really not found any positive evidence.  Minnesotans is a state with active political dialogues.  Senator Paul Wellstone and his fellow Democrat and current Governor Mark Dayton were two of the few Senators who voted against authorizing the use of force in Iraq and the rest is history.  Unnecessary wars, massive military spending, and an ongoing drone war carried on by the Obama administration.  The longest continuous period of warfare in the history of the USA.  The end result is that we are in a continuous war against terrorists,  continuous cyberwarfare against China and Russia, and we are current seeing significant military build ups by those same countries.  All of this against the backdrop of President Eisenhower's remarkable farewell address to the nation televised January 17, 1961.  The relevant sections include (my emphasis added):

"..........A vital element in keeping the peace is our military establishment. Our arms must be mighty, ready for instant action, so that no potential aggressor may be tempted to risk his own destruction.

Our military organization today bears little relation to that known by any of my predecessors in peacetime, or indeed by the fighting men of World War II or Korea.

Until the latest of our world conflicts, the United States had no armaments industry. American makers of plowshares could, with time and as required, make swords as well. But now we can no longer risk emergency improvisation of national defense; we have been compelled to create a permanent armaments industry of vast proportions. Added to this, three and a half million men and women are directly engaged in the defense establishment. We annually spend on military security more than the net income of all United States corporations.

This conjunction of an immense military establishment and a large arms industry is new in the American experience. The total influence -- economic, political, even spiritual -- is felt in every city, every State house, every office of the Federal government. We recognize the imperative need for this development. Yet we must not fail to comprehend its grave implications. Our toil, resources and livelihood are all involved; so is the very structure of our society.

In the councils of government, we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the military industrial complex. The potential for the disastrous rise of misplaced power exists and will persist.

We must never let the weight of this combination endanger our liberties or democratic processes. We should take nothing for granted. Only an alert and knowledgeable citizenry can compel the proper meshing of the huge industrial and military machinery of defense with our peaceful methods and goals, so that security and liberty may prosper together........"      

Eisenhower was a genius -  decades ahead of the current thinking on conflict-of-interest and its problematic results.  Going beyond the famous reference to the military industrial complex, Eisenhower's speech was about balance, conservation, and mutual respect. Disarmament described as being necessary because another war could destroy civilization. It was a speech made by a military expert turned statesman - balanced and very reasonable.

But despite Eisenhower's best intention, the American military has marched on with three unnecessary wars in my lifetime and continued record amounts being spent on the machinery of war.  In 2105 the US spent $596 billion dollars - more than the next 7 nations combined.  The Department of Defense is the largest single employer in the world.  The defense budget has long been the subject of cost overruns and overspending.  The word corruption is rarely used appropriately in American politics, but what would Eisenhower call  a $640 toilet seat?  From that same timeline - cost overruns alone add an additional 25% to the cost of weapons systems.  It seems clear that top down management massive budgets in a political atmosphere dominated by funding concerns, lobbyists, and special rules that favor the major parties is a recipe for inefficiency at best and corruption at the worst.

Parallels between what happens to the military budget and healthcare funding are undeniable.  In health care - the politics is clearly on the side of large businesses that were put in place as proxies by the federal government for containing costs - despite the clear evidence that has not happened.  Professional organizations also lobby they are generally ignored relative to business interests.  Per capita health care spending in the US is roughly 40% more than the next highest nation with no incremental increase in quality and much worse access to health care.  All of this mismanagement flows from politicians and bureaucrats at federal and state levels who talk about the constant need to reform health care.  The only notable reforms have been the use of large health care companies as inefficient proxies for government control,  selective rationing of specific areas of health care like psychiatric and addiction services, ballooning administrative costs, and placing an intense, costly level of administrative control over the physicians who are delivering the service.  Instead of learning from the past 30 years, the managers at all levels are doubling down with more requirements and regulations.  We have an endless supply of $640 toilet seats in the health care system and at the same time entire states where a person cannot get adequate treatment for an addiction or a psychiatric problem.  The government and business side of the equation needs to cling to the myth that this type of management is necessary, despite the fact that it was unequivocally demonstrated in 1998 that it was not and the more important long term trend that these business managers add no value to the system as all - apart from what they can make up as advertisements.

Does that sound like a system that can manage foreign policy or military strategy?  Somewhere along the line Americans are led to believe that we have competent military leaders who are advising Congress and the Executive branch.  In order to accept that advice a lot of political demagoguery that occurred in the election campaigns must be set aside.  A lot of past mistakes must be acknowledged and corrected.  A lot of the accusations about immoral and criminal behavior do not inspire the confidence of Americans or other citizens around the world. The scare tactics about whose finger is a safer finger to put on the nuclear button needs to be stopped and a more sober discussion about stepping back from high alert nuclear status and disarmament needs to happen.  Warfare and aggression should never be the default position.

The major difference between the military and healthcare funding is that the financial drain on the averagae family for military funding is less transparent that healthcare.  With costs being transferred to the working class under high deductible plans, the average retired couple paying and average $250K in retirement for healthcare, and now exploding costs for Obamacare, working class families are tired of paying excessive amounts for healthcare.  Any head of household who has survived the tech bubble stock market crash, the housing bubble crash, and the associated Wall Street scandal where hardly anyone was prosecuted and all of the major players were essentially unfazed.  Everybody knows some working class person who ended up fined or sent to jail for cheating the IRS.  It is also common knowledge that these infractions are trivial compared with tax breaks and questionable financing by the affluent.

Although the major parties have certainly played a role in orchestrating this dramatic fiasco - they don't bear complete responsibility.  At many levels American culture is poorly equipped to deal with tough problems.  There is a love of technology but a focus on impoverished data sets.  There is a limited understanding of current problems and potential solutions.  The best solutions are rarely reached by political compromise and the end to those arguments typically results in wrapping oneself in the flag and declaring that there has never been a better system (or country) invented.

Rather than putting it all behind us and uniting behind the next President like we all traditionally do - I hope this ugly campaign gets Americans contemplating the larger issues instead of what is commonly referred to as "the narrative".  We need to get back to the real story itself rather than the narrative.  The issues are there and they are not going away just because some politician is trying to buy your vote with money, a job, an empty promise, or special interest politics.  The issues are there no matter how we get "handled" by the managerial classes.

That is what we all have to keep in focus.

George Dawson, MD, DFAPA  

Supplementary 1:

I filed the above piece on Election Day, at least 8 hours before the New York Times election site started to predict that Donald Trump had a "greater than 95% chance" of winning the Presidential Election.  Since then I have been shocked at the number or reasonable people who are outraged by the election result and suggesting that this election is an indictment of the American character.  I won't list the specifics but they are easily viewed elsewhere.  Maybe I am just a hardened Minnesotan who can still clearly remember when professional wrestler named Jesse Ventura shocked the major parties in the state by being elected Governor.  Looking at the debates he had with those candidates - the outcome should have been predicted.  Both the Democrat and the Republican in that race found themselves agreeing Ventura on most of the major topics.  As I drove into work the next day, I listened to a major party legislator predict a catastrophe due to a professional wrestler rather than a career politician.  And guess what?  No catastrophe - in fact - a seamless transition.  The Governor's Office ran well.  Ventura's  only error (and it was a big one) was not to make the most of this victory and prove once and for all that the major parties can be superfluous in the process.

The failure of the polls to predict the election result, is instructive for any students of sampling and statistics.  If the sample is inadequate, don't print the headlines based on the inadequate sample.  I don't think the second question about that has been answered yet.  That question would be whether enough people are "off the grid" or uncooperative with the sampling process enough to make these polls predictably unpredictable.  Is it safe to say it was a failure of Big Data?

From what I know about the political process I see this playing out a few ways:

1.  Trump makes a seamless transition to office in a manner very similar to Ventura.  It will actually be easier for a Trump transition because he is technically a Republican,  even though many Republicans clearly dislike him.  Ventura was a member of the Independence Party and both parties disliked him and yet he was able to form a reasonable cabinet and nobody noticed that there was not a Democrat or a Republican in office.  He maintained a populist position by provided tax rebates.  The real potential for damage from a Trump administration will be a ballooning federal deficit, but even then it is a matter of degree.  There is no way that any Democrat or Republican will establish a precedent of actually paying for the expenditures on their watch.

2.  I have been stunned by the naivete that some people have about how men talk.  Trump's 'locker room" talk is what I am referring to.  I had a discussion last week about this very issue.  One opinion was that this kind of talk was a "generational thing" - in other words done only by dinosaurs like me.  I have certainly talked with men of all ages who refer to women in a crude manner.  I certainly don't use those terms myself and never have.  I don't "approve" of these references, but I also realize that men who talk that way are certainly not waiting on my approval.  I know this type of discussion exists.  I also know the meta-language involved.  In other words, the language has different meanings in different contexts like most language does.  I will let the linguists come up with a detailed analysis, but at the common sense level it is clear that a lot of people could ignore it.

3.  Trump has been conciliatory in his early remarks since the win.  The key question at this point is whether he can maintain that demeanor.  If he does not become antagonistic and uncompromising he has a great opportunity to seen what he can accomplish. From the political debates, it was clear that the Trump campaign was more about process and rhetoric that it was about content and a mastery of the issues.  He needs to take a lesson from Governor Ventura about what not to do when you unexpectedly get into office.

4.  Most but not all of the pundits seem to have missed the point that a lot of the Trump emotionality was directed at the working class and the working class has not fared well in American politics for decades.  Wages are flat, unions have disappeared, health care costs have increased and were set to explode with Obamacare.  Against that backdrop, the major parties have really done nothing but shore up Wall Street.  The working class has been a traditional mainstay of the Democrats.  As my grandmother used to say" "They are for the little guy!"  That has not seemed to be the case to me for a long time.

5.  Most Trump supporters do not take him literally - this is my speculation and it is in direct opposition to opposition to other more radical theories of the motivations of Trump supporters.

Just a few early observations about why a Trump presidency is not necessarily a catastrophe and also - how it happened.....