Phenotypic diversity from dogs to diseases

 

Whether you are trying to keep your neighbor’s German shepherd out of your yard or avoiding that biting Chihuahua on your way to the mail boxes – people have no problem identifying domestic dogs. Most can tell they are not foxes, wolves, or coyotes. There are approximately 400 different domestic dog breeds worldwide – but they all have the same taxonomic classification.

All domestic dogs belong to the same genus and species according to Linnean classification and that is Canis familiarus.  The genus was established in 1758 by Linnaeus to include dogs, wolves (C. rufus, C. lycaon, C. lupus, C. lupaster, C. simnesis) , coyotes (C. latrans), and jackals (C. aureus).  Foxes belong to the genus Vulpes and there are 12 species. This genus forms a clade meaning that they are all descended from a common ancestor.

Domestic dogs can be traced back to 15,000 to 100,000 years ago when they were originally descended from the Gray Wolf in East Asia (1).  Breeding programs have been used to select specific physical and behavioral characteristics of domestic dogs that had led to the observed phenotypic diversity.  The domestication process in general has selected for genetic changes and associated changes at the neurobiological level.  High prevalence illnesses are observed in some dog breeds suggesting that there are heritable loci that could be studied and provide some guidance for human diseases.  Purebred dogs can also have extensive genealogies including family histories and pathology data. 

In terms of comparative genomics (1) there are 4 clades of placental mammals  Afrotheria: ( elephants, manatees, and hyraxes), Xenartha: (sloths, anteaters, and armadillos),  Euarchontoglires: Euarchonta (primates, tree shrews, colugos) + Glires (rodents and lagomorphs), and Laurasiatheria: (shrews, hedgehogs, bats, and other carnivores including dogs).  The most extensively studied mammals at the genetic level all belong to Euarchontoglires (human, chimpanzee, mouse, rat). More detailed information on the dog genome allows for analysis for sections of conserved human DNA, reconstruction of the genetics of a common ancestor between clades, and investigations into the nature of polygenically determined illnesses.

One of the most interesting aspects of reference 1 is the phylogenic tree of the family Canidae showing the relationships between different phyla. This tree was constructed looking at 12 exons (8,080 base pairs (bp) and 4 introns (3029 bp). They were sequences in 30 of the 34 Canid species.  Note where domestic dogs are on the diagram. The boxer photo is used because the boxer genome was the prototypical analysis in this paper because it has some of the longest stretches of homozygosity (62%).  In the diagram clades are color coded (see legend). Each cladogram is constructed with Bayesian analysis generating the respective bootstrap values from Markov chain analysis and posterior probabilities (see legend for location). Indels are insertions-deletions.  Divergence times are in millions of years and are applied to the wolf-like clade discussed in the paper (color coded blue).   

The authors constructed a map of 2,559,519 SNPs (single nucleotide polymorphisms).  They were able to determine the SNP rate for domestic dog breeds and other Canids (wolves and coyotes) and determined it was essentially 1 SNP per 900 (bp) base pairs for all the dog breeds studied except the Alaskan malemute (~1/790 bp).  Wolves and coyotes had greater variation than dogs suggesting a bottleneck during dog domestication.   The authors also demonstrated limited haplotype diversity within dog breeds.  The boxer genome was shown to have homozygosity over 62% of the genome with long blocks having the same haplotype on both chromosomes. The authors looked at the haplotype structure and linkage disequilibrium (LD) across 224 dogs – 10 each from ten breeds and one each from an additional 24 breeds. They used this analysis to construct a population genetics picture of dogs. Among the conclusions is that the dog genome is older (9,000 generations) than the human genome (4,000 generations).   

This is probably a good spot to briefly discuss homozygosity and why that is important.  In terms of experiments. It reduces interindividual variation based on genetics.  Laboratory rats for example have nearly identical genomes after 20 crosses (sib-sib, parent-offspring).  There is a previous post on this blog that discusses stochastics based on behavioral variation in rats with nearly identical genotypes. Dog breeding is a variation on that theme. Dogs do not have the same high degree of homozygosity but they are in the intermediate range.  The majority of dogs in the US are not pure bred but are of mixed heritage.  They can still inherit morphological and behavioral traits as well as genetically based diseases.   The human genome has a lower level of homozygosity due to widespread migration from a common ancestor about 150,000 years ago, a longer life span, as well as cultural constraints such as limits on consanguinity or marriage or a reproductive relationship between two closely related individuals. In the case of marriage by first cousins there is data on consanguinity rates between countries. The medical concern with this practice is that as homozygosity increased the risk of genetically determined autosomal recessive illness increases. Autosomal dominant conditions remain problematic but are not contingent on inheriting identical genes from both parents.   

Species	Homozygosity - same alleles inherited from each biological parent
Norwegian Rat Rattus norvegicus	1: Considered genetically identical at 20 generations of crossbreeding but some heterozygous alleles can be found out to 40 generations. (7) 2:  Rat breeds (phenotypes) are analogous to dog breeds – as an example the albino lab rat is still Rattus norvegicus. 3:  Experimental results on one inbred colony cannot be generalized to the next.
Domestic dogs Canis familiarus	1:  Degree of homozygosity varies with breed and specifics of breeding procedure for pure bred dogs.  Pure bred dogs – 63% homozygosity (10) Mixed breed dogs – 53% homozygosity (10)
Humans Homo sapiens	1: 11% homozygosity in individuals who parents were first cousins (consanguineous) compared with the expected value of 1 out of 16 or 6% (8) applying basic models 2:   Range of homozygosity in humans is wide based on evolutionary factors (bottlenecks, founder effects, inbreeding, outbreeding, background relatedness).  Runs of homozygosity (ROH) are studied more often than whole genome comparisons.

 

In summary, the genetics of domestic dogs is interesting just considering the phenotypic diversity of Canis familiarus.  It highlights issues of classification and that have been discussed in many places on this blog. Students of biology are familiar with these issues from practically every course they have ever taken.  That does not appear to be the case for people who never studied these problems.  Medicine and psychiatry as branches of biology have similar degrees of freedom on an individual basis and for classification purposes.  Any physician knows that no two persons with the same diagnosis are identical and yet there are scores of critics, administrators, politicians, and healthcare companies operating under that illusion. There are similar illusions about social constructs describing some subpopulations.  All humans are still Homo sapiens.  Further subclassification at the genomic or molecular level may be possible but it does not negate the meaning of the Linnean classification.  

In terms of temperament, personality, and behavioral characteristics correlations exist at the genetic level.  Since most of the behavioral traits are polygenic in nature – they have to be considered very early results.   

 There are probably as many advocates that claim a diagnosis has a simplified meaning that they are either advocating for or against.  Socially constructed classifications like race are more problematic.  The basic observation that hundreds of obviously different looking dogs belonging to the same genus and species may drive the phenotypic diversity point home.  The fact that these dogs breeds are also morphologically and behaviorally diverse as well as the fact that that develop unique diseases – provides a potential opportunity for studying morphology and disease mechanisms in humans. Despite suggestions about dog being potential models for human neuropsychiatric disorders that may be too strong of an association.  The research I did for this post was interesting from an evolutionary and genomic standpoint.  It highlights potential genetic and neurobiological effects of domestication as a selective breeding process.

Considering the application of a similar phenotypical diversity concept to complex diseases – why would we not expect hundreds of phenotypes?  Current analyses seem to suggest very simple phenotyping.  In the case of major depression – a single item from a rating scale – emotional blunting or anhedonia and genetic correlates. Other complex diseases like asthma, systemic lupus erythematosus, and diabetes mellitus have similar problems.  On the other hand, we can look at the combinatorics of the verbal descriptions of depression and how many of those combination exist in a clinical population and find 126 subtypes of depression. The question for me is why a handful of rating scale phenotypes of depression would exist and not 126 or more? The same is true for any psychiatric disorder. And of those 126 or more types – what is happening at the genetic and molecular levels?  The idea of a better classification based on some verbal hierarchy or rearranging the verbal descriptions does not seem promising to me.  The dilemma of trying to classify natural phenomena by words is always a limitation. There is no better example than biological classification.       

 

George Dawson, MD, DFAPA

 

 

Graphics Credit:  From reference 1 with permission - Copyright Clearance Center License Number 6004620929064

 

References:

1:  Lindblad-Toh K, Wade CM, Mikkelsen TS, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005 Dec 8;438(7069):803-19. doi: 10.1038/nature04338.

2:  Bergström A, Stanton DWG, Taron UH, et al. Grey wolf genomic history reveals a dual ancestry of dogs. Nature. 2022 Jul;607(7918):313-320. doi: 10.1038/s41586-022-04824-9. Epub 2022 Jun 29. PMID: 35768506; PMCID: PMC9279150.

3:  Spady TC, Ostrander EA. Canine behavioral genetics: pointing out the phenotypes and herding up the genes. Am J Hum Genet. 2008 Jan;82(1):10-8. doi: 10.1016/j.ajhg.2007.12.001.

4:  Parker HG. Genomic analyses of modern dog breeds. Mamm Genome. 2012 Feb;23(1-2):19-27. doi: 10.1007/s00335-011-9387-6. Epub 2012 Jan 10. PMID: 22231497; PMCID: PMC3559126.

5:  Hecht EE, Kukekova AV, Gutman DA, Acland GM, Preuss TM, Trut LN. Neuromorphological Changes following Selection for Tameness and Aggression in the Russian Farm-Fox experiment. J Neurosci. 2021 Jul 14;41(28):6144-6156. doi: 10.1523/JNEUROSCI.3114-20.2021.

6:  Rahim NG, Harismendy O, Topol EJ, Frazer KA. Genetic determinants of phenotypic diversity in humans. Genome Biol. 2008 Apr 24;9(4):215. doi: 10.1186/gb-2008-9-4-215. PMID: 18439327; PMCID: PMC2643926.

7:  National Research Council (US) International Committee of the Institute for Laboratory Animal Research. Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the 1998 US/Japan Conference. Washington (DC): National Academies Press (US); 1999. Genetic and Phenotypic Definition of Laboratory Mice and Rats / What Constitutes an Acceptable Genetic-Phenotypic Definition. Available from: https://www.ncbi.nlm.nih.gov/books/NBK224550/

8:  Woods CG, Cox J, Springell K, Hampshire DJ, Mohamed MD, McKibbin M, Stern R, Raymond FL, Sandford R, Malik Sharif S, Karbani G, Ahmed M, Bond J, Clayton D, Inglehearn CF. Quantification of homozygosity in consanguineous individuals with autosomal recessive disease. Am J Hum Genet. 2006 May;78(5):889-896. doi: 10.1086/503875. Epub 2006 Mar 21. PMID: 16642444; PMCID: PMC1474039.

9:  Bell JS.  Genetic diversity.  Accessed on March 24, 2025 https://www.akcchf.org/assets/files/Genetic-Diversity_Bell-2021.pdf

10:  Pemberton TJ, Absher D, Feldman MW, Myers RM, Rosenberg NA, Li JZ. Genomic patterns of homozygosity in worldwide human populations. Am J Hum Genet. 2012 Aug 10;91(2):275-92. doi: 10.1016/j.ajhg.2012.06.014. PMID: 22883143; PMCID: PMC3415543.

11:  Shearin AL, Ostrander EA. Leading the way: canine models of genomics and disease. Dis Model Mech. 2010 Jan-Feb;3(1-2):27-34. doi: 10.1242/dmm.004358. PMID: 20075379; PMCID: PMC4068608.

12:  Amfim A, Bercea LC, Cucu N. Canine Genetics and Epidemiology of Behavior in Dogs. Epizootics-Outbreaks of Animal Disease: Outbreaks of Animal Disease. 2025 Feb 5:105.

13:  Ilska J, Haskell MJ, Blott SC, Sánchez-Molano E, Polgar Z, Lofgren SE, Clements DN, Wiener P. Genetic Characterization of Dog Personality Traits. Genetics. 2017 Jun;206(2):1101-1111. doi: 10.1534/genetics.116.192674. Epub 2017 Apr 10. PMID: 28396505; PMCID: PMC5487251.

14:  Friedrich J, Strandberg E, Arvelius P, Sánchez-Molano E, Pong-Wong R, Hickey JM, Haskell MJ, Wiener P. Genetic dissection of complex behaviour traits in German Shepherd dogs. Heredity (Edinb). 2019 Dec;123(6):746-758. doi: 10.1038/s41437-019-0275-2. Epub 2019 Oct 14. PMID: 31611599; PMCID: PMC6834583.

15:  Handegård KW, Storengen LM, Joergensen D, Lingaas F. Genomic analysis of firework fear and noise reactivity in standard poodles. Canine Med Genet. 2023 Mar 8;10(1):2. doi: 10.1186/s40575-023-00125-0. PMID: 36890545; PMCID: PMC9996964.

16: Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD, Lohmueller KE, Zhao K, Brisbin A, Parker HG, Vonholdt BM, Cargill M. A simple genetic architecture underlies morphological variation in dogs. PLoS biology. 2010 Aug 10;8(8):e1000451.

17:  Morrill K, Chen F, Karlsson E. Comparative neurogenetics of dog behavior complements efforts towards human neuropsychiatric genetics. Human Genetics. 2023 Aug;142(8):1231-46.

18. H. J. Noh et al., Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder. Nat. Commun. 8, 774 (2017). doi: 10.1038/s41467-017-00831-x; pmid: 29042551

19. N. H. Dodman et al., A canine chromosome 7 locus confers compulsive disorder susceptibility. Mol. Psychiatry 15, 8–10(2010). doi: 10.1038/mp.2009.111; pmid: 2002940820

20. K. L. Overall, Natural animal models of human psychiatric conditions: Assessment of mechanism and validity. Prog. Neuropsychopharmacol. Biol. Psychiatry 24, 727–776 (2000). doi: 10.1016/S0278-5846(00)00104-4; pmid: 11191711

Preventing Dementia and Blood Pressure Control

 

A paper came out last week (1) that showed blood pressure control was an effective way to prevent dementia.  One of the most effective ways to prevent stroke is to control blood pressure.  Elevated blood pressure also causes blood vessel damage that can lead to dementia – even in the absence of a clearcut stroke. In one of my clinics, we assessed people with various forms of dementia and it was striking how many people had these kinds of changes on their CT or MRI scans and were unaware of them. In some cases, there was a history of uncontrolled blood pressure like eclampsia during pregnancy that probably resulted in brain changes seen decades later that was not investigated at the time.  Substance use problems, undiagnosed forms of transient hypertension, and substance use problems with intoxication and withdrawal associated hypertension are other possibilities.

The study in question was an interventional study across 163 villages in China and a total of 33,995 research subjects. Inclusion criteria into the study was ≥40 years of age with a mean untreated SBP ≥140 mm Hg and/or a DBP ≥90 mm Hg (or ≥130 mm Hg and/or ≥80 mm Hg among those with clinical CVD, diabetes or chronic kidney disease) or a mean treated SBP ≥130 mm Hg and/or a DBP ≥80 mm Hg, based on six measurements taken on two different days. Additional details are available in the paper on online supplementary information.  Patients were treated across the study by physician supervised non-physician community healthcare providers (NPCHPs).  Research subjects were randomized into treatment as usual (TAU) or non-protocol-based treatment for hypertension and protocol-based care. In the protocol-based care patients received first line antihypertensives like angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretic or diuretic-like medications. The treatment group also got free blood pressure medication, lifestyle coaching, and home blood pressure monitors but the TAU group did not.

The primary outcome measures for this intervention study were the presence of dementia and cognitive impairment no dementia (CIND).  Both diagnoses were made by expert panels of neurologists using standardized criteria.  Screening tests were administered at clinic visits to assess cognition, instrumental activities of daily living, and symptoms of dementia in a standard way. 

On the main outcome measures the blood pressure intervention group had a 15% lower risk of dementia and a 16% lower risk of CIND compared with the TAU group.  Those numbers are consistent with an additional meta-analysis done by the authors of similar trials and a previous meta-analysis of blood pressure interventions to prevent dementia.

Strokes are the usual obvious consequences of blood pressure problems and they come in two forms – hemorrhagic and ischemic. Hemorrhagic strokes generally occur through a ruptured blood vessel in the substance of the brain or the subarachnoid space.  Because blood is under very high pressure in the brain that jet can cause additional damage.  In many cases clots form and they can be associated with edema and pressure in the brain. Symptoms can vary from an intense headache to signs of cerebral edema or coma and death.  Ischemic strokes consist of blood vessel occlusion or reduced blood flow to the point that there is inadequate blood supply to neurons. This can occur as the result of ruptured plaques, emboli, or mechanical disruption of the blood vessel.  The emboli can be the result of plaque formation in blood vessels as well as blood clots due to other diseases like atrial fibrillation.  Atrial fibrillation can also be caused by hypertension.

During my teaching seminars on dementia and vascular subtypes – I generally taught about vascular subtypes as cortical or parenchymal infarctions due to major blood vessels (yellow areas on the above diagram), lacunar infarctions due to damage to long perforating arteries to the striatum (pink area), and small vessel ischemic disease or Binswanger’s Disease (BD) due to deep arterioles supplying the subcortical white matter (blue area).  Although BD was described in 1895 it has been a controversial diagnosis that has not been clarified by modern brain imaging and the presence of white matter changes ofet referred to as “white matter ischemic changes” by radiologists.  The diagnosis is also complicated by the fact that many patients has features of both Alzheimer's Disease (AD) and BD and in some cases AD, BD, and small infarctions at autopsy.  If there is any confusion about the diagnosis, a history of hypertension, previous treatment for hypertension, a review of all previous brain imaging, and the clinical pattern of changes in cognition and functional capacity should all be described.   

I am restricting my comments in this post to how hypertension results in dementia so I will not comment on the differential diagnosis of stroke.  Elevated blood pressure can also cause blood vessel damage that is not due to a rupture or embolism.  Prolonged hypertension can cause inflammation in long blood vessels supplying the striatum and periventricular white matter in the brain.  The specifics of that process are being actively studied at this point but damaged is hypothesized to occur because of endothelial cel dysfunction as well as compromise of elastin a connective tissue protein in blood vessels leading to inflammation and narrowing or expansion of blood vessels.  The inflammatory process can lead to further changes and result in a compromised blood-brain barrier and progressive narrowing of those blood vessels.  Eventually the circulation is compromised resulting in the death of neurons visualized as volume loss and white matter changes on imaging studies.   

There seems to be very little work done on the actual pressure signaling at the level of the blood vessel.  Many physiological studies and reviews are focused on overall blood pressure effects and the effect of pressure waves within the vascular system. There are other determinants of endothelial dysfunction including the effects of aging, toxins like tobacco smoke, intercurrent diseases, and metabolic/nutritional factors like blood glucose, lipids, and uric acid.  Epidemiological data supports resting blood pressure and pulse pressure as being significant factors leading to endothelial dysfunction and atherosclerosis.

The modern approach to treating the problem of endothelial dysfunction leading to cardiovascular and cerebrovascular disease is to address all the risk factors.  Hypertension, smoking, diabetes mellitus, metabolic syndrome and obesity, dyslipidemia, and substance use including alcohol all need to be addressed. Many psychiatrists might see this as a primary care problem – but given the way health care is rationed these days a psychiatrist may be the only physician that the patient is seeing on a regular basis.    

That provides the opportunity to collect data like weight, blood pressure and pulse, as well as metabolic parameters if needed. One of my previous posts discusses the issue of blood pressure parameters and white coat effect, and white coat hypertension. The previous thinking was that a lot of people get hypertensive just from the stress of being in a physician’s office.  Some research backed that up showing no difference in outcomes. That research had the same design problems as research about the safety of alcohol.  The control group contained people with cardiovascular diseases and treatment for hypertension. The practical way to address this issue is to advise the patient to check their blood pressure at home with an approved device. Many of these devices can download data into a smartphone app for easy storage.  Home blood pressure monitoring is also useful to detect Transient blood pressure increases due to physical or emotional stress. Although it has not been well studied – this kind of blood pressure reactivity probably needs to be addressed since acute and chronic increases irrespective of etiology are a problem.  

Age is one of the most significant risk factors for dementia. As the incidence of dementia increases with more survivors into old age – there are early interventions that can prevent it from happening.  Good blood pressure control happens to be one of them. 

George Dawson, MD, DFAPA

Supplementary on Binswanger:

Otto Binswanger (1852-1929) was a Swiss physician.  Like many brain specialists of the day he was variously described as a psychiatrist, neurologist, and neuropathologist. He identified as being a psychiatrist primarily but in those days before board certification psychiatry was a much broader field. Both Freud and Meyer had similar qualifications. He is sometimes confused with his nephew Ludwig Binswanger (1881-1966) who was one of the leading researchers of the existential psychiatry movement.  He described “encephalitis subcorticalis chronica progressive” while attempting to differentiate types of dementia from dementia caused by tertiary syphilis that was called general paresis of the insane or GPI at the time.  GPI was a very common reason for institutionalization at the time accounting for 20% of admission and 34% of the death in asylums in the 19^th and early 20^th century before the advent of antibiotics.

Binswanger’s description was controversial up to modern times and I will try to capture that in the graphic below.  The original description was published in 3 issues of a trade paper rather than a medical journal.  It is often critiqued as being long, rambling, and not publishable by today’s standards.  I think that criticism has the benefit of the retroscope since most papers at the time would have similar difficulties.  

Supplemental references on the Binswanger graphic according to those dates:

1894:  Blass JP, Hoyer S, Nitsch R. A translation of Otto Binswanger's article, 'The delineation of the generalized progressive paralyses'. 1894. Arch Neurol. 1991 Sep;48(9):961-72. doi: 10.1001/archneur.1991.00530210089029. PMID: 1953422.

1910:  Dening TR.  Stroke and other Vascular Disorders – Clinical Section.  In: A History of Clinical Psychiatry. Berrios G, Porter R (eds). New Brunswick.  The Athlone Press. 1995: 72-85.

1910:  Nicolson M.  Stroke and other Vascular Disorders – Social Secition. In: A History of Clinical Psychiatry. Berrios G, Porter R (eds). New Brunswick.  The Athlone Press. 1995: 86-94

1986:  Esiri MM, Oppenheimer DR.  Diagnostic Neuropathology. Blackwell Scientific Publications, London, 1896.

1994:  Hansen LA. Pathology of Other Dementias.  In:  Alzheimer Disease.  Terry RD, Katzman R, Bick KL (eds). New York. Raven Press. 1994: 167-196.

The discussion of neuropathology in this text and the subsequent edition is superior to what is seen in general pathology texts and some neuropathology texts.

Román GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993 Feb;43(2):250-60. doi: 10.1212/wnl.43.2.250. PMID: 8094895. 

2025:  Bir SC, Khan MW, Javalkar V, Toledo EG, Kelley RE. Emerging Concepts in Vascular Dementia: A Review. J Stroke Cerebrovasc Dis. 2021 Aug;30(8):105864. doi: 10.1016/j.jstrokecerebrovasdis.2021.105864. Epub 2021 May 29. PMID: 34062312.

 

References:

1:  He J, Zhao C, Zhong S, Ouyang N, Sun G, Qiao L, Yang R, Zhao C, Liu H, Teng W, Liu X, Wang C, Liu S, Chen CS, Williamson JD, Sun Y. Blood pressure reduction and all-cause dementia in people with uncontrolled hypertension: an open-label, blinded-endpoint, cluster-randomized trial. Nat Med. 2025 Apr 21. doi: 10.1038/s41591-025-03616-8. Epub ahead of print. PMID: 40258956.

2:  Supplementary Information for Reference 1 (see Supplementary Table 7. Meta-Analysis of Randomized Controlled Trials of Antihypertensive Treatment on Dementia) for results of 5 additional RCTs of hypertension treatment in dementia.  https://www.nature.com/articles/s41591-025-03616-8#Sec23

3:  Franklin SS, Thijs L, Hansen TW, O'Brien E, Staessen JA. White-coat hypertension: new insights from recent studies. Hypertension. 2013 Dec;62(6):982-7. doi: 10.1161/HYPERTENSIONAHA.113.01275. Epub 2013 Sep 16. PMID: 24041952.

4:  Lockhart SN, Schaich CL, Craft Set al. Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi-Ethnic Study of Atherosclerosis (MESA). Alzheimers Dement. 2022 Apr;18(4):551-560. doi: 10.1002/alz.12429. Epub 2021 Sep 5. PMID: 34482601; PMCID: PMC8897510.

Listening with the Third Ear….

 

I joined a group co-teaching a resident seminar in psychotherapy a few weeks ago.  It is an interesting exercise blending didactics and experience.  The format is an hour of psychodynamic focused didactics followed by an hour-long discussion of a transcript by everyone in attendance including residents and 4 faculty. That is an interesting discussion of the technical aspects of therapy as well as individual differences in interpretation and intervention.

Today’s session was about listening and how listening in therapy may be different from what people consider to be typically focused or unfocused listening.  There was some discussion of how you listen to friends as opposed to strangers.  There was a secondary discussion of the depth of listening with a focus on unconscious determinants.  It led me to reflect on a couple of things during the session.

The first was focus.  Very early in my discussion with patients I was focused on what they were saying.  My focus was the same focus I would have with friends or family even though none of my patients would ever enter that sphere. People knew that I was serious and took them seriously.  As I thought about the way I interacted with people over the years – it was apparent that even though patients are technically not friends within a very short period, I would know more about them than I knew about most of my friends.  In some cases, I was more worried about them and spent more time worrying about them than I ever worried about most of my friends. The difference was in the relationship.  With friends there is a mutual affiliation and expectation of support.  In the case of patients – the relationship is for the benefit of the patient. Apart from payment, the gratification of doing good work,  and the occasional thank you -  the therapist should expect nothing back from the patient. 

The focus in both diagnostic interviews and psychotherapy was meditative to me.  I felt extremely comfortable in that setting.  I looked forward to seeing people.  It was the place in life where I felt the most comfortable. I was not particularly interested in one problem compared with another – just hearing every unique story.  When you get to a certain point in your career you are full of confidence.  You no longer have to worry about running into an issue that you don’t know how to address. You know that most people will leave your office feeling better than when they entered – even if it is an initial evaluation. 

Focus in a psychiatric interview is multifaceted.  It involves hearing both the content of what is being said and whether it makes any sense.  Do all the elements hang together in a cohesive picture or not?  If not, the job is to immediately clarify what is happening.  That always leads me back to think of an Otto Kernberg seminar that I attended 30 years ago.  Kernberg described the process of confrontation as exactly that – an indirect inquiry that would facilitate bringing these seemingly disparate elements together.  An extreme example that I frequently use is from acute care settings.  In those settings, my first task of the day was to interview people who had been admitted on involuntary holds.  They were often very angry to be hospitalized and demanded to be released. Their first words were typically: “I want you to discharge me.  You have no right to hold me in this hospital and I want to be discharged.”  The reality is that I had never seen the patient before.  I had nothing to do with how they came into the hospital or the fact that they were on an involuntary hold. Restating those facts to the patient was the type of confrontation Kernberg discussed and it most frequently led to a more productive reality-based conversation.

The focus for me always has the elements of attention, testing what is being said against my internal knowledge of reality and doing the same with any emotional content, and thinking about underlying theories for what I am seeing. At times I will explicitly ask the patient for their theories about what is happening to them to see if they have any and if they do whether they are plausible.  It is generally important to try to figure out the meaning of certain patterns of thought and behavior including dreams fantasies, and other potential unconscious content.

There is also a focus of kindness toward the patient.  The relationship is one of beneficence.  It always reminds me of Jerry Wiener’s comments about the essence of psychotherapy “Be kind and say something useful to the patient.” When I bring that up – many therapists bristle at the apparent oversimplification.  Kindness does get directly to the point that the therapeutic relationship is different from the patient’s perspective in that they should experience the therapist as unique relative to the common experiences in their life. Some therapists I have encountered over the years have talked about “reality therapy” to mean that the therapist should be reacting to what the patient does just like everybody else.  This misses one of the main advantages of psychotherapy as an opportunity to examine what is really going on in those other relationships and correct it if necessary.        

I addition to attending to the primary problem in sessions the therapist must also have a focus on the relationship and empathic responses to communicate to the patient that he had an adequate understanding of the mental problem that the patient is describing and what all the elements may be.  The relationship aspect may include the stimulus value of the therapist and how that varies with age, sex, physical appearance, and communication style.  To cite age as an example – it is common for early career psychiatrists just out of residency to be greeted with: “You are too young to be a psychiatrist.  I have never seen a psychiatrist as young as you are”. Those statements come with varying degrees of enthusiasm and carry several implications that can be explored.  On the other end of the spectrum I have not had anyone comment on my advanced age directly – but have heard comments that some doctors are so old “they did not know I was in the room.” 

Transference and countertransference are obviously relevant here but I want to stay with the focus in interviews and sessions.  In the seminar today, a paleontology metaphor was described about mining the different layers of the unconscious and how to get there.  That suggests a lot of heavy lifting to me. I see it as a much more dynamic situation.  After all – here I am extremely comfortable and interested listening to people and editing their comments for plausibility, cognitive and emotional content, defensive patterns, and their own theories about what may be happening to them.  Together we are defining what brought them in to see me along with all the relevant cultural, social, biological, and developmental factors.  This is all unfolding in the context of a specially defined relationship.  Throughout that session I am switching between listening mode and an interventional mode that involves supportive, clarificatory, and interpretive remarks.  That switching needs to be dynamic, context based, and is not the same for any two patients.  There is also the practical or real relationship including payment arrangements, appointment times, call instructions, and emergency contact instructions.

There is a check that must happen during or between sessions. Every therapist has to ask if they really understand what this patient is saying and if the patient is being helped.  That check can occur as early as the first interview.  In some cases, the therapist may consider the patient’s problem to be outside of their field of expertise. This can also happen after prolonged therapy where the benefit to the patient is uncertain – but they want to continue the therapy.

The title of this blog post refers to a famous book called Listening with the Third Ear by psychoanalyst Theodor Reik. I purchased the book in 1986 on the recommendation of one of my psychotherapy supervisors.  The subtitle of the book says it all: “the inner experience of the psychoanalyst.”  Reik was one of Freud’s first students.  In the chapter “The Third Ear” he describes attending to various cues of the unconscious life of the patient as well as what may prevent the analyst from perceiving them. He illustrates how the subjective reaction of the analyst to the patient can be one of those clues.

Reflecting on this essay so far – the one dimension that needs additional commentary is the non-linear nature of listening and the interview process. It is easy to think of the process as a matrix dependent on focused attention and a long sequence of questions.  That is the format of a structured interview. In many cases these interviews are algorithmic based on hierarchies and inclusion and exclusion criteria.  In a clinical and psychotherapy setting the focus is more on all aspects of the presenting problem. What the patient brings in to the session and the continuity over multiple sessions is more of a priority. Reik describes a patient who caused him to feel annoyed, two different patients walking by a mirror outside his office and how they react to the mirror, and the way a patient looked at him as well and what that meant for their unconscious life. 

In a subsequent chapter he goes on to describe how the analyst must avoid selective attention to what they might want to hear and how they must attend to everything.  He points out that Freud used the term gleichschweben  that has the connotation of equal distribution and revolving or circling (p. 157).  He suggests the terms freely floating and poised attention.  He adds Freud’s rationale for this type of attention as being two-fold.  First, it avoids exhaustion since it is impossible to attend to anything for an hour.  Secondly, it avoids biasing the interview or session toward a particular aim or goal.  The session after all is directed at what the patient is deciding is relevant.

As I revisited my technique, this captures what I tend to do in interviews and sessions. Since I read this book nearly 40 years ago – I cannot claim to have invented it.  I can add a little to what Reik and Freud have to say especially in diagnostic interviews.  It is possible to incorporate free-floating attention and transition to a more structured interview as necessary. Most psychiatric practices these days require that psychiatrists seen anywhere from 2 to 5 new patients per day.  Most of those patients will not be seen in either psychoanalysis or psychodynamic psychotherapy. But most of those patients will benefit from the listening techniques and interventions that can be attributed to the early analysts. It is also possible to add a psychotherapy component to practically every patient seen by a psychiatrist over time – even in relatively brief appointments.  

 

George Dawson, MD

 

References:

Reik T.  Listening with the Third Ear. Farrar, Strauss, and Giroux. Toronto. 1948: 144-172.

 

Supplementary 1:  Both Drs. Otto Kernberg and Jerry Wiener in the above essay are psychoanalysts with extensive teaching and publication experience. They are both medical doctors.  I left the qualifications out for the sake of brevity. I heard Dr. Wiener’s remarks at one of the Aspen Psychotherapy Conferences organized by Jerald Kay, MD.   

Supplementary 2: According to Reik, The metaphor listening with the third ear was borrowed from Nietzsche -  Beyond Good and Evil, part VIII, p.246.  A partial excerpt follows:

"What a torture are books written in German to a reader who has a THIRD ear! How indignantly he stands beside the slowly turning swamp of sounds without tune and rhythms without dance, which Germans call a "book"! And even the German who READS books! How lazily, how reluctantly, how badly he reads! How many Germans know, and consider it obligatory to know, that there is ART in every good sentence--art which must be divined, if the sentence is to be understood! If there is a misunderstanding about its TEMPO, for instance, the sentence itself is misunderstood!..."

The Demon Haunted World – A Survivalist Counterfactual

 

The Demon Haunted World – A Survivalist Counterfactual

 

I found myself watching survivalist videos last night.  I had just completed a blog post and was working on another (that is becoming a thesis rather than a blog) and decided to take a break.  I have dabbled in that literature on and off over the past 30 years and found that it does not add much. The end games are typically played out in popular movies and fiction. You either find yourself in an impregnable underground shelter or wandering semi-aimlessly over a barren and hostile landscape.  Both scenarios have their problems.

In the impregnable fortress there are the inevitable power struggles, equipment breakdowns, outside attacks, functional and dysfunctional alliances, and lack of planning.  Good recent examples include The Silo and Fallout.  In the wandering scenario there seem to be a plethora of hazards including violent psychopaths, cannibals, various zombies, diseases, natural disasters, and the ever-present lack of food and water.   Examples include The Road, The Walking Dead, and The Last of Us.

Survivalists are more realistically focused. The brief series that I watched emphasized escaping detection by any means.  The implication was that you were in a secure remote location with adequate food and water.  The assumption is that there are many people who were not prepared for when the shit hits the fan or WTSHTF for short.  Four days of starvation is enough to make most people desperate and at that point they cannot be trusted.  A corollary is that once they get skilled at taking what they need from others – you may be the next target.

The first video discussed the importance of smoke. A poorly constructed fire can lead to a smoke signal for people to see for miles.  That signal translates to shelter, warmth, food, and resources to any desperate person who sees it.  The author emphasized methods to minimize smoke production. Elaborate underground survival shelters not only minimize smoke but also heat signatures to avoid infrared detectors and missiles.

 The second avoidable signal to the post-apocalyptic miscreants is gunfire. You might be thinking hunting, but the emphasis was on interpersonal conflict rather than hunting.  There may be better ways to resolve a dispute and secondarily gunfire WTSHTF is not necessarily a red flag. It is a sign out there that somebody has food and resources they want to protect.   The zombie mindset is “even if you do not have a gun – you might be able to hang around in the darkness long enough to get what you want.”  No other ways were discussed about how to avoid gunfire.

The final avoidable signal was light.  Even as little as a candle represents somebody with enough resources that they can and want to see in the dark. It represents the last vestige of civilization.  For that reason, it must be blocked at all costs. Curtains were emphasized as a practical measure but black out screens were preferable.  It reminded me of the subtitle to Carl Sagan’s classic book The Demon Haunted World (TDHW).  That subtitle is: Science as a candle in the dark.  It seemed like a perfect metaphor for what is currently happening in the world. To anyone who has not read the book – the subtitle is from Thomas Ayd’s 1655 treatise on witchcraft A Candle In the Dark where he described witchhunts as a way to delude the people about what was otherwise unexplainable.  Sagan sums up the progress against witchmongering this way:

“Microbiology and meteorology now explain what only a few centuries ago was considered sufficient cause to burn women to death.” (p. 26).

The title is a metaphor for reason and truth in the context of dire superstition and this is captured by Sagan’s summation.

Many reviews of TDHW suggest that Sagan’s views are formulaic – a few rules about how to assess facts and be skeptical along with listing logical fallacies. That minimizes the context he provides about the founding fathers and how they were impacted by The Enlightenment and science. Sagan’s thesis is more complex. He is the first to acknowledge that science is not perfect but that the method of science encourages and produces self-correction. To capture reasoning that is strictly outside of formal science, Sagan suggests that all matter of human endeavor like politics, economics, and even specific policies can be subjected to scientific reasoning and scrutiny and it will result in better results and prevent primitive biases.    

Since the beginning of the COVID-19 pandemic there has been an almost continuous attack on science and scientific experts.  The first Trump administration attacked public health officials, physicians, scientists, and anyone affiliated with them.  They promoted ineffective and potentially harmful treatments for COVID, suggested vaccines were problematic, said that COVID-19 was no worse than the flu, and that case and death rates were overstated.  Several conspiracy theories were promoted suggesting that HIV was a planned bioweapon, that NIH officials were corrupt, and that the “planned” HIV epidemic was paralleled by the “planned” COVID epidemic.  If the COVID epidemic was not planned it was supposed to have originated from a lab leak in China despite all the evidence pointing against that.  The problem is not merely a lack of training in science and the scientific method.  The problem is that we have a large segment of the population that really does not care about their ignorance of science and a large segment who seem to happily take advantage of that on social media.

Sagan has a famous quote that is considered prophetic by many:

“…Science is more than a body of knowledge; it is a way of thinking.  I have a foreboding of an America in my children’s or grandchildren’s time – when the United States is a service and information economy; when nearly all the key manufacturing industries have slipped away to other countries; when awesome technological powers are in the hands of a few, and no one representing the public interest can even grasp the issues; when the people have lost the ability to set their own agendas or knowledgeably question those in authority; when, clutching our crystals and nervously consulting our horoscopes, our critical faculties in decline, unable to distinguish between what feels good and what’s true, we slide almost without noticing, back into darkness and superstition.”   (p. 25).   

Much has been made about manufacturing in the US and there is an active debate.  Specifically – is it a feasible solution for whatever economic problems you claim it will solve?  I have seen business experts interviewed who say it is not and others who have their own specialized supply chains within the country as being a solution. How will it be compounded by tariffs and an attempt to resuscitate the coal industry? The technological power is concentrated at the monopoly level according to several court decisions.  And what about artificial intelligence? There are daily predictions that AI will replace not only truck drivers and assembly line works but also doctors and teachers.  There are grandiose claims that AI will "cure all diseases" in less than the time I have been writing this blog.  Those aspects of Sagan’s prediction seem too uncertain to be useful.

The lack of knowledge in both the general population and at the highest levels of government is also on display.  Scientific knowledge and thinking is lacking and that it is not enough.  Any reasonable analysis of population wide policies needs to include a scientific dimension, a rational thinking dimension, and a moral/ethical dimension.  This is the real current failure.  As an example, the divisive rhetoric used around the COVID-19 issue.  There was a lot of uncertainty about the best way to stop the pandemic. As physicians and public health officials were learning about this and saving lives – the counter response was that no measures were necessary including vaccinations.  In the end public health officials were being blamed for lockdowns and school closings that could only have been done by local elected officials. That rapidly evolved to conspiracy theories that led to threats of physical harm and legal action against some of the top scientists.  The culmination of this rhetoric was recently evident when the Trump administration replaced a government webpage providing scientific information on COVID-19 with one that presents a combination of conspiracy theories and pseudoscience.  None of this sequence of activity included science, rationality, or ethics.

This is what Sagan is referring to in his quote. The current web page on COVID is emblematic of sliding into the modern version of darkness and superstition. Like the old version the new one is as out in the open and accepted by many. There is an army of celebrities, podcasters, media networks, social media bots, and writers supporting it. Some of the wealthiest people in the country claim they were “censored” because they opposed some suggested COVID measures or supported anti-science rhetoric – even though there was no formal censoring. The dark narrative is very present and it continues to take its toll in terms of cabinet appointees who promote it and some who seek vindication against scientists and officials who were making a good faith effort.

As far as science goes, whether that is hard science or the dismal science of economics – we have a choice to stay in darkness and superstition or move toward the light of science and facts.   Not caring about the smoke is the difference between surviving and living.

 

 

George Dawson, MD, DFAPA

 

 

Graphics Credit:

Campfire in the forest by Crusier, CC license BY-SA 3.0 https://creativecommons.org/licenses/by-sa/3.0&gt https://commons.wikimedia.org/wiki/File:Campfire_in_forest.jpg

References:

1:  Sagan Carl.  The Demon-Haunted World – Science as a Candle In The Dark.  Ballantine Books 1997.

2:  Ayd Thomas.  A Candle in the Dark.  Smithfield, London. 1655.

Cannabis and Psychosis in the 1980s - and since...

 

I thought I would commemorate one of the first papers I read on this issue when I became an acute care psychiatrist in 1988 (1).  It was my third year out of residency.  I started working on an acute care unit at St. Paul-Ramsey Medical Center in St. Paul, MN.  It was the highest acuity setting I have seen anywhere since then.  It was a combined unit that treated all forms of acute psychosis including affective psychoses and drug induced states.  There was also a forensic component so there was a lot of aggression and violence. There was no shortage of street drugs and even though it was 37 years ago – I have not seen more cases of hallucinogen and stimulant induced psychosis anywhere. I had the occasion to treat a patient who had a pocket full of PCP.  There were the more typical cases of alcohol and sedative withdrawal.  It was where I started to observe the connection between cannabis use and acute psychosis.

Like any compulsive psychiatrist fresh out of training – I was taught to study my patients’ conditions and find current literature. The very first paper I found was an observational study of Swedish army conscripts, their psychiatric conditions, cannabis use, and long-term psychiatric outcomes (1). It was also my introduction to registry studies that happen in Scandinavian countries.  Everyone in the population is on the same database so it is easy to follow them over time and look at outcomes.  In this case 45,470 draftees in the Swedish army were followed for 15 years.  Two questionnaires were administered at baseline – one to look at psychosocial determinants and risk factors for mental illness and the other for substance use history. The sample who refused to complete the substance use history were eliminated from the study. 

All the subjects were given an unspecified structured interview, psychological tests, and were seen by a psychologist.  Any subject with psychiatric symptoms were seen by a psychiatrist and any diagnosis determined was per the ICD-8 nomenclature.  The cohort was followed through a national registry of psychiatric care from 1969/1970 to 1983.  Psychiatric admissions and deaths were followed per the respective databases.   Cannabis consumption was documented as number of episodes of use with subjects using cannabis 50 or more times classified as heavy users. 

 Relative risks were calculated for estimated number of uses compared with a nonuse group and higher risk was noted at both the low and high ends. One lifetime use conferred a risk of 2.4 relative to no use.  For heavy lifetime use, the risk was 6 times greater than no use.  There was a dose dependent increase in cases of schizophrenia for the intermediate levels of use in between.

Of the other variables that were examined, several were noted to increase risk including psychiatric diagnosis at baseline, general childhood adversity, and school adjustment. 

In their discussion, the authors review possible explanations for the association with a schizophrenia diagnosis including cannabis use as causal, cannabis use as non-causal but psychiatric disorder causing cannabis use, and cannabis use as precipitating schizophrenia only in that subgroup of the population who are genetically and developmentally predisposed. They cite their own findings that show of the total number of schizophrenia cases – only 21/274 were in the high consumption group and only 49/274 had ever tried cannabis.  They conclude that cannabis was “an additional clue to the still elusive aetiology of schizophrenia.”  In their references, the authors have 12 case reports or series of cannabis induced psychosis dating back to 1972.

That was my introduction to the literature on cannabis, psychosis, and schizophrenia back in the late 1980s.  I had the good fortune to work with people who were admitted to my units for psychosis who were heavy cannabis users over the next 22 years.  I observed several patterns:

1:  Cannabis induced psychosis – this was probably the easiest to diagnose.  The patient is acutely intoxicated on cannabis and that resolves with detoxification.  The only further treatment that may be required is if the patient has a substance use disorder.

2:  Repeated episodes of psychosis that eventually do no resolve with detoxification -  these are generally heavy cannabis users and they typically have cannabis use disorder or uncontrolled use of cannabis. There have no pre-existing psychiatric diagnosis or family history of severe psychiatric disorders.  The most sensitive marker of heavy use was generally daily use but the specific method of use (blunts, spliffs, dabs) was also a sign.  These patients require treatment for psychosis for stabilization.  The duration of that treatment had to be individualized.

3:  Pre-existing psychiatric disorders exacerbated by use – recurrent episodes of psychosis in patients with a pre-existing diagnosis of schizophrenia, bipolar disorder, or depression with psychosis preceded by cannabis use is a very common problem.

As a clinician the practical approach to sorting out where cannabis fits into the scheme for psychosis and schizophrenia is a detailed evaluation and often getting to know the patient over time through repeated clinic visits or hospitalizations. The short-term goal is stabilizing them enough for hospital discharge with a plan to minimize or eliminate recurrent episodes.  If they can abstain from further cannabis use, gradual reduction and discontinuation of any medication required for stabilization is indicated. Educating the patient and their family about the psychotogenic potential of cannabis and referral for substance use treatment is also required.  That general outline is always dependent on other factors like severity of the episodes and patient preference.

One of the pieces left out of the debate on psychosis and cannabis use is the Naranjo scale.  This scale was developed in 1981 (2,3) to give the probability of an adverse event based on certain parameters. Just looking at the sequence of events I have described here – the relationship between cannabis and psychosis is probable to definite according to this scale.  The relationship to schizophrenia is less certain based on the fact it is a longitudinal diagnosis.

The treatment of cannabis induced disorders has been confounded by the widespread hype about cannabis in the American culture.  As an example – there are people who insist that you cannot develop uncontrolled consumption of cannabis, that it cannot cause psychosis, and that it is good for your mental health. There is scant evidence that any of those statements are true. After I changed to a strictly outpatient practice for the last 12 years, it was obvious that anxiety, depression, and insomnia were frequent problems related to cannabis use. At that time I was seeing a population with substance use problems.  The argument could be made that both major populations I treated over the course of my career had significant selection biases.  I would be the first to acknowledge that is true.  Those selection biases do not negate 35 years of very close observation often corroborated by many team members and collateral history. 

The issue of cannabis toxicity is highly politicized.  Like most things in the US, there are special interests set up to make a lot of money off cannabis and related compounds.  They have expected political and media influence. The idea that cannabis was a “medical” intervention was ultimately the rhetoric that led to legalization – even though there is negligible evidence that it is useful for any medical application.  I used to say that cannabis has been used by humans for over 6 centuries – what are the odds that there is an undiscovered miracle medical application?  I am willing to say that most people can probably smoke it and get high with the usual risks of any other intoxicants that includes accidents, injuries, and death.  The cannabis defenders will always say it is safer than alcohol. That is an argument based on low prevalence use.  As cannabis use picks up to the point where it is used as much as alcohol or more – the adverse outcomes including health outcomes will multiply.  I consider psychosis, exacerbations of pre-existing psychotic and other psychiatric disorders, addictions, lung disease, and cardiovascular disease to all be potential adverse outcomes.

Those are all the hard lessons I learned working with people who had these adverse effects over 35 years.  It all started for me with reference 1.

 

George Dawson, MD, DFAPA

 

References:

1:  Andréasson S, Engström A, Allebeck P, Rydberg U. Cannabis and schizophrenia a longitudinal study of Swedish conscripts. The Lancet. 1987 Dec 26;330(8574):1483-6. Full Text

2:  LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548069/

3:  Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2):239-45. doi: 10.1038/clpt.1981.154. PMID: 7249508.

Image Source:  English: CC 2.0 Attribution: please credit "Elsa Olofsson" and attribute a link to the original source of the image at: CBD Oracle.

Date   4 October 2020, 13:46:42

Source: https://www.flickr.com/photos/189516854@N06/50610714018/

Author:          elsaolofsson

 

Supplementary 1: There have been hundreds of references to cannabis induced psychosis in the literature since I first read this one.  I may take that on at some point - but I do not expect much modification to the initial results.  Human biology requires one to think probabilistically. Some people - even if they have the genetic constituents that make them vulnerable will not develop the condition being studied or they will develop it at a later time.  And of course without the vulnerability the probability of developing the condition is much lower to non-existent.  Those observations from genetics and biology can apply to the original study making the etiology of psychosis from cannabis less "elusive." 

Supplementary 2:  My go to interview questions for heavy cannabis use involved asking about daily use and type of use (how the smoke was delivered). Many of those questions were subsequently validated in a structured research interview for cannabis use.

Supplementary 3:  Naranjo scale for estimating the probability of an adverse drug event (see reference 2 for details).

The Tech Bros Want to Replace Your Teachers and Doctors

 

 

Just last week I was contacted by an acquaintance about Viagra.  He was not a physician and got the prescription through an online business that specializes in dispensing hair loss, erectile dysfunction, anxiety, and depression medications. When I see these businesses advertising that combination of medications it always piques my interest. Why these medications? Comparing them with the most prescribed drugs in the US – 3 antidepressants are in the top 20 - sertraline, trazodone, and escitalopram.  They can double for anxiety medications.  Viagra (sildenafil) is 157 and Cialis (tadalafil) is 172.  Finasteride can be used for both hair loss and prostatic hypertrophy and it is number 72.  Topical minoxidil is not on the list. It is not like there is a shortage of prescriptions for any reason.

My contact person had talked with one of the online prescribers and was not sure about how he was supposed to take the medication. Should he take it every day or just on the days he was going to have intercourse?  Reading the prescription label and the information he was sent was not helpful.

More of these online prescribing services seem to be advertising every day.  They promise cost effectiveness, the same medications that your physician would prescribe, ease or use, and no embarrassment.  How many times have you been in line at your clinic or pharmacy and had a staff person belt out some information about you that you preferred stay private?  That line on the floor separating you from the other patients is not enough distance to muffle a receptionist shouting through plexiglass.  The online service promises to send you the medication in a plain brown wrapper. 

The real downsides to this new relationship are never mentioned. No access to your records to check for contraindications, drug-drug interactions, pre-existing medical conditions, the status of your liver and kidney function, or allergies. No access to your physician who may know you so well that they can say if taking a new medication would be advisable or not. No detailed discussions of risks, potential benefits, and unknowns. For me that discussion has taken longer than most of the telemedicine visits I have heard about.  And most importantly – no access to somebody who knows your situation if something goes wrong.

There is a real issue about how much information these rapid online prescribers keep on file and what it is used for.  Do they list your major medical conditions?  Does that lead to marketing? Does that lead to data mining to develop sufficiently large programs to make more money off you?  Recall that wherever your data is on the Internet, somebody is trying to profit from it.

That brings me to a stark conclusion about capitalism that I discovered too late in life. Growing up in the US, you are sold on the idea that capitalism and democracy are the mainstays of the country.  We are special because of both and we do both better than anyone else in the world.  The wealthy are idealized and everyone aspires to be wealthy.  If you can't get wealthy maximizing your material possessions seems to be a substitute.

American products are good because our environment producers entrepreneurs and competition among entrepreneurs produces superior products.  Think about that for a second.  The entrepreneur gets all the credit.  Forget about all of the science and engineering behind any product.  The faceless people laboring behind the scenes are hardly ever mentioned. If you are industrious enough, you might be able to find out who holds the patents but in the end they are all property of a large company.  And that company is there for one reason – to make as much money as possible.

In a service industry like medicine corporate profits were initially hard to come by because it was a cottage industry of private physicians.  Even as the corporate takeover began in the 1980s, physicians resisted to some extent as a powerful mediating class between corporate interests and the interests of physicians and patients. The end run around that physician mediation was hiring them as employees.  Initially corporations proposed that they were going to make primary care more accessible and minimize specialists.  In the end that was merely a tactic and they acquired specialty care as well as primary care.  Today most physicians are employees and have minimal input to their practice environment.  They are essentially told by middle managers how to practice medicine.  They work by default for companies like managed care companies and pharmacy benefit managers that waste physician time to rubber stamp their rationing procedures. 

The profits from the corporate takeover of medicine are high.  It is after all a recipe for making money.  There is a stable subscriber base fearful of medical bankruptcy and the corporation can decide how much of those funds it wants to spend. In thinking of new ways to make more money, telemedicine is the latest innovation. Convenience is a selling point. It has been used for decades to reach people in rural areas who would have a hard time travelling long distances to clinics.  But the current model is more like Amazon online shopping.  If you have condition x, y, or z – contact us and we will get you a prescription. Better yet, let’s take the pharmacy middle man out of the picture and prescribe and sell you the medication at the same time.    

A recent commentary in the NEJM pointed out the potential problems of the new relationship between pharmaceutical companies and telehealth firms (1). It is as easy to imagine as the following thought experiment.  Suppose you are watching a direct-to-consumer ad about a weight loss drug.  You go to the suggested web site where it tells you to make a telehealth appointment the same day for a nominal fee. One study showed that 90% of patients referred through this sequence got a prescription for the advertised drug.  The pharmacoepidemiology, quality of care, and legal ramifications of these arrangements are unknown.  The scrutiny is nonexistent compared with the claims that physicians were being influenced for decades by free lunches.  That matches my suspicion that the physician conflict of interest hype was more a political tactic than reality to suppress any objections to the political and corporate takeover of medicine.  

That brings me to the Bill Gates (2) comment.  Expectedly he is an unabashed promoter of computer technology and the latest version – artificial intelligence or AI.  His thesis is that AI will commoditize intelligence to the point that humans will not be necessary for most things including teaching and medicine. No mention of the conflict of interest.  The company he founded – Microsoft is currently heavily marketing computers with an early version of AI. A couple of years ago they also changed to a license for life model.  In other words when you buy a Microsoft computer or software package – you no longer own it outright.  You must pay a monthly licensing fee if you use it or if they decide not to support your computer any more – you must upgrade it to continue paying monthly fees for a long as you use your new computer.  Or until they tell you again that you have to buy a new one.  Even though intelligence is “free” Microsoft and all of the other major tech companies are not really giving it away – they have a recipe for making money off of you for the rest of your life.   

There is a reason that doctors don’t know much about business or politics. Both are highly corrupting influences. Medicine is a serious profession that is squarely focused on mastering a large volume of information and technical skill and keeping that current. Businesses on the other hand are focused on every possible way they can get your money and they are very good at it. If it comes down to an AI program providing medical care that is all you really need to know.

 

George Dawson, MD, DFAPA

 

References:

1: Fuse Brown EC, Wouters OJ, Mehrotra A. Partnerships between Pharmaceutical and Telehealth Companies - Increasing Access or Driving Inappropriate Prescribing? N Engl J Med. 2025 Mar 27;392(12):1148-1151. doi: 10.1056/NEJMp2500379. Epub 2025 Mar 22. PMID: 40126465.

2:  Richards B.  Bill Gates Says AI Will Replace Doctors, Teachers and More in Next 10 Years, Making Humans Unnecessary 'for Most Things'.  People Magazine March 29, 2025.  https://people.com/bill-gates-ai-will-replace-doctors-teachers-in-next-10-years-11705615

 

Graphic Credit:

Click on the graphic directly for full information on the Wikimedia Commons web site including CC license.  It is used unaltered here.