Trump Derangement Syndrome - Will It Become a Mental Illness in Minnesota?

 

It came to my attention yesterday that a bill has been proposed in the Minnesota Legislature to declare Trump Derangement Syndrome a mental illness.  Anyone unfamiliar with the mental illness statutes in Minnesota might ask why there are definitions like that in the law in the first place. The purpose of these definitions is threefold as far as I can tell. First, they define the behavioral evidence in terms of severity necessary to meet the standard of severe mental illness.  In common parlance that is typically described as risk to self, risk to others, or inability to care for oneself because of mental illness.  No diagnostic criteria or reference to diagnostic manuals is made. The definitions are there as lay standards so that potentially any interested person can act on them. Second, they are necessary criteria for civil commitments, guardianship, and conservatorships in the state. In other words, a psychiatric diagnosis by itself is not sufficient criteria for any of those proceedings.  The statutory requirements must also be met.  Finally, the criteria also determine eligibility for additional treatment resources like case management and outreach services.     

To confirm the validity of this proposal I sent emails to both of my state representatives Rep. Elliot Engen (R) and Sen. Heather Gustafson (D). I expressed my concern that the mental health statutes in the state are for the serious business of civil commitment, guardianship, and conservatorship proceedings and therefore I needed to know if Trump Derangement Syndrome was a serious proposal and if it was – what they were going to do about it.

I have not heard back at this point but the press coverage is increasing so I will talk about it as if it is legitimate.  Where does this come from and what does it really mean?  During the previous Trump election there was a lot of controversy about whether he had a psychiatric diagnosis – primarily a personality disorder.  There was a lot of discussion about narcissistic and antisocial personality disorders. There were several high-profile psychiatrists and some academics who maintained these positions.  These criticisms still surface today.  At the time, I critiqued those positions based on the APA’s Goldwater Rule.  Psychiatric profiling was invented by Jerrold Post, MD for intelligence gathering and it was not meant to be applied to politics.  The Goldwater Rule states that a direct assessment must be done and any information released with informed consent.  Those controversies basically faded because the public criticism had no impact and it was obvious that a lay standard in the 25^th Amendment rather than public speculation is the overriding consideration:

“Section 4:

Whenever the Vice President and a majority of either the principal officers of the executive departments or of such other body as Congress may by law provide, transmit to the President pro tempore of the Senate and the Speaker of the House of Representatives their written declaration that the President is unable to discharge the powers and duties of his office, the Vice President shall immediately assume the powers and duties of the office as Acting President.”    

Even though a substantial number of Trump’s first staff disapproved of his performance or thought he was incompetent – there was no effort to invoke the 25^th Amendment.  He was subsequently rated as the worst President to date by polled historians.  We also learned that if the President or his party control the Supreme Court – it is possible that an entirely different standard applies than it does to the average citizen. It is clearly possible that the President can commit crimes and escape prosecution. 

The idea that Trump is an unlikeable person is easily explored with the following thought experiment.  How many people like liars? Trump is described as lying an unprecedented amount in the history of American politics – tens of thousands of lies.  At times the lies are characterized as bullshitting using Frankfurt’s philosophical definition.  According to Frankfurt - bullshitters have more disregard for the truth than liars.  So, pardon me if you think bullshitting is more acceptable.  How many people object to a person who routinely calls other people names and ridicules the disabled?  How many object to threats?  How many object to racism, misogyny, and white supremacy? How many object to withdrawing foreign aid amounting to less than 1% of the budget if it results in the deaths of hundreds of thousands of people (3.3 million according to a New York Times estimate from AIDs, malaria, TB, lack of vaccinations, and a lack of food).  How many people like the administrative, justice, public health, and research infrastructure of the United States being decimated on an arbitrary basis by Trump appointed designees?  How many people like loyal government employees working in non-political positions in the US Postal Service, the Veteran’s administration, and the National Park System terminated either for a completely fictional cause or without cause?  I think the point is made even though this is only a partial list of what Trump has done to cause people to legitimately dislike him.  I could probably come up with a much longer list.  For completeness sake – let me add – how many people like a President who attempted to overthrow the US government and who has continued to lie about the election for the next 4 years?

That brings me to the statute:

Subd. 28.Trump Derangement Syndrome.

"Trump Derangement Syndrome" means

2.24 the acute onset of paranoia in otherwise normal persons that is in reaction to the policies

2.25 and presidencies of President Donald J. Trump. Symptoms may include Trump-induced

2.26 general hysteria, which produces an inability to distinguish between legitimate policy

2.27 differences and signs of psychic pathology in President Donald J. Trump's behavior. This

2.28 may be expressed by:

2.29

(1) verbal expressions of intense hostility toward President Donald J. Trump; and

2.30

(2) overt acts of aggression and violence against anyone supporting President Donald

2.31 J. Trump or anything that symbolizes President Donald J. Trump.

        

On the face of it – this definition is poorly written by people who are obviously not mental health professionals. The wording can be taken as colloquial rather than technical.  That means the terms “paranoia” and “hysteria” are whatever the politicians decide to use them for and that could include name-calling. Concern about the Trump on-again off-again tariffs?  You are just paranoid. 

The idea that these meaningless expressions would cause “an inability to distinguish between legitimate policy differences and signs of psychic pathology in President Trump’s behavior” is laughable.  First, as previously noted nobody is making any psychiatric diagnoses on Trump.  That time has passed.  His party is more than willing to let him do whatever he wants.  Second, it does not take a mental health professional to decide if someone is unlikeable, or doing things that you do not like, or using rhetoric that you do not like, or is conducting themselves in an immoral or unethical way that you do not like.  We all do it every day.  We are all judged on our behavior every day and accountable in many ways.  The vague wording in the preamble in this statutory language is intentional and it gives the proponents plenty of freedom to determine what they think is “intense hostility” toward Trump.  They could at least include a scale using examples of Trump’s intense hostility to others. As hostile as Trump was to Zelensky in the tragic White House meeting or possibility some of his milder name calling incidents directed at Clinton, Harris, or Obama?  The essence of this language is that it sends the strong message that if you criticize Trump – you are at risk.  He is basically beyond criticism even though he is the most objectionable President on record.  The “overt acts of aggression and violence…” language is already illegal without this nonsensical modification.

Like most things in the Trump administration there is no scientific backing to any of this language.  The rhetoric is slightly more interesting. Anyone paying causal attention to the news has seen the pattern of outrage followed verbal aggression (mainly name calling and lying) that is a standard part of MAGA theatrics over the past several years. If you really have not - just turn on one of their news channels, podcasts, or radio broadcasts. Better yet – attend a school board meeting and witness the screams about book banning and other things that are often not even happening. More recently that has spilled over into MAGA town halls meetings to the point that the GOP has had to shut them down.  Other than the obvious appeals to excessive and inappropriate emotion in these meetings there are two additional patterns that cannot be missed.

The first is what I like to call the gangster approach to pseudo negotiation. This was evident in the meeting between Zelensky, Trump, and Vance. Before any actual content was discussed both Trump and Vance were accusing Zelensky of “not respecting them” or saying “thank you’.  This is what you will find in any rapper beef but it obviously has no place in high level diplomacy.  What were Trump and Vance trying to do here?  To anyone familiar with rhetoric, this is a standard attack on the person rather than their argument. Zelensky never got his argument out and then to add insult to injury he was told to leave the White House as if he had really done something wrong.

The second is a variation on that theme. Whenever Trump is even mildly confronted, he acts like he has been wounded.  One of his comments is “You are not very nice; you are not being very nice to me.”  He will rationalize the rest of his behavior such as refusing to talk or attacking the journalist or their organization based on that sensitivity.  He will often attack the journalist typically by calling them names or questioning their ability.  In some cases, he will suggest that the interviewer has some nefarious purpose or that they are part of a “fake news” conspiracy against him.  In more recent developments he is suggesting that the people in the media who he does not like will be prosecuted.

Both patterns are obvious in the news and in life. We typically encounter this kind of behavior as adolescents from bullies in schools. Recall that bully on the playground who likes to make up nicknames for classmates just to humiliate and embarrass them. He persists in using the nickname even though you and your friends don’t like it.   You all acquiesce because he is bigger and will beat you up if you protest too much. Occasionally some smaller kid stands up to the bully and punches him in the nose.  At the meeting with the principal – the bully and his father claim the other kid started the fight.  They are typically outraged and tearful.

That is the real reason for a Trump Derangement Syndrome statute.  It allows even more leverage against the people who protest the bully.  Now some politician can gaslight them in addition to Trump bullying them and calling them names.  

This is not a mental illness.  It is a political tactic.  It is an affront to anyone with a real mental illness, their caregivers and treatment providers. If this language is allowed to stand in Minnesota it adds to the embarrassments that this administration has placed on the American people and will result in a gaslighting defense for America’s number one bully.

 

George Dawson, MD, DFAPA          

To editors: I have a more concise 500 word version of this essay that could be published if there is an interest and the publication seems right.  Contact me if you are interested.  

Supplementary 1:  There still is a possibility that this proposal is a hoax. If that is true there will be a predictable response from Republicans suggesting that this response is just another example of Trump Derangement Syndrome.  Their rhetoric can be cancelled by pointing out that their technique of flooding the zone is really just another application of Brandolini's Law and it is unfortunate that they do not devote as much energy to serious governing.

Supplementary 2:  The parallels between patterns of authoritarian suppression in Russia/USSR and the current administration are unmistakable.  Non-medical and political "diagnoses" are widely used to suppress and detain dissidents and other targets of political oppression. In the US, the current administration is making strong initiatives to suggest any criticism of the President is illegal as well as many forms of legal protest.  

Graphic:

The graphic in this case is taken directly off the Minnesota Revisor web site – an official site of the state government.  The link I used is available below – but it disappears and gets updated to a new link frequently:

 https://www.revisor.mn.gov/bills/text.php?number=SF2589&version=0&session=ls94&session_year=2025&session_number=0 

 

More Than You Wanted to Know about Bird Flu and Chickens...

 

Are chicken flocks only culled in the US?

I ran into typical MAGA disinformation on the Internet the other day.  The post stated "not a single chicken" had been killed in Canada or Mexico due to the bird flu compared to millions in the US.  Since all the social media sites have been captured by MAGA I decided to debunk the claim that only flocks of chickens with avian influenza in the US are culled and not chickens in Canada or Mexico.  After reading pandemic misinformation for the past 5 years – it seemed like this was going to be an easy task and I was not wrong.

The latest North American bird population estimates were about 7 billion birds in 529 species in 2019 (1,2).  That represented a decline of about 3 billion birds since 1970.  Habitat loss, ecosystem destruction, and climate change were considered significant factors according to these authors. Anthropogenic threats like collisions with vehicles and other manmade structures, poisoning, and predation by domestic animals was also estimated to be a significant factor. Domestic cats kill roughly 1.3 to 4 billion birds annually (3). By comparison the estimate of bird deaths from contact with windmills is about 140,000 – 328,000 annually (4).      

Considering the chicken population in all 3 countries – the US has a total of 1.53 billion chickens annually that includes 1.2 billion broiler chickens alive at any one time and about 350,000 egg laying chickens. The total chicken population in Canada is 173.94 million.  In Mexico the total chicken population is 611.2 million.

Meat, poultry, and egg production in the US is regulated by the USDA and the Poultry Products Inspection Act (PPIA).  That includes other poultry like geese, ducks, guinea hens, and other more exotic domesticated birds.  In Canada it is the Canadian Food Inspection Agency (CFIA).  In Mexico it is the Ministry of Agriculture and Rural Development.  The culling of domestic chickens because of avian influenza has become a contentious political issue and a source of right wing misinformation. Additional misinformation has included blaming the Biden administration for culling chickens and driving up egg prices. The question of how these decisions get made, especially when large numbers of infected chickens are euthanized has been answered by experts in the past.  Here is one quote from CBS News when asked about the loss of 148M poultry since 2022:

"It's a staggering number, there is no doubt," said Jodie Guest, a professor of epidemiology with Emory University's Rollins School of Public Health in Atlanta. "But it is, and always has been a policy across administrations, with the USDA, that this is how they handle infections like this among poultry. And as we've seen bird flu move [across] species, it becomes even more important to try to contain that infection in the flocks that it's in, so that we don't continue to see spread."

The USDA has an infographic on measures to contain avian influenza outbreaks.  From that page “Birds are destroyed usually within 24–48 hours of detecting the disease. USDA pays for birds that must be destroyed.”  The cost of a live chicken can range from $5 to $20.  There seems to be a question about whether infected birds need to be euthanized.  This is the rationale provided by the American Veterinary Medical Association (AMVA):

“Recovery of poultry from HPAI is extremely rare. Infected poultry typically are euthanized and poultry products destroyed when HPAI infection is confirmed. The outcome also may be influenced by the producer’s participation in secure food supply plans. If regulatory officials authorize you to treat, keep in mind that the FDA prohibits extralabel use of adamantine and neuraminidase inhibitor classes of antiviral drugs in chickens, turkeys, and ducks.”

HPAI in this case is Highly Pathogenicity Avian Influenza defined as causing high mortality in poultry and are H5 and H7 influenza viruses.  Not all viruses belonging to those classes are highly pathogenic.  There are also Low Pathogenicity Avian Influenza (LPAI) viruses that may not cause any symptoms in affected birds.  There is the possibility that LPAI viruses can mutate into HPAI viruses and they are monitored for that reason. In the US – ill or deceased domestic birds are typically reported at the state level to animal health officials. They decide what level of analysis needs to be done and recommend protective measures.  Any casual historical search of previous outbreaks in avian populations will also reference significant culling of domestic fowl in all three countries. 

In the US, 148M domestic birds have been euthanized due to the latest outbreak of avian influenza including 20M egg laying chickens.  Exact numbers of euthanized poultry in Mexico since 2022 are harder to come by but are in the millions.  In Canada the number is about 14.5M.  I have not found a site that examines the differences in euthanized poultry between countries.  Variability will depend on wild bird exposure, total populations of domestic birds exposed, size of the domestic flock, biosecurity measures, and farm density. 

In summary, there is a consensus about approaches to HPAI in domestic birds. There is really no evidence that either Canada or Mexico does not recommend euthanizing infected birds.  There is no evidence that significant numbers of domestic fowl have not been euthanized in both countries currently and during past HPAI pandemics. From a veterinary medicine standpoint, it does not make sense – because most of the HPAI infected population dies and they act as a source for further mutations and facility contamination. The discrepancies in the total populations euthanized in all 3 countries occur because of policies (reimbursement for dead birds in the US), levels of oversight (state and federal in the US), and varying levels of reporting.  There is no evidence that the culling of birds is due to a political initiative or an initiative to adversely impact the economy.  And why would any rational President want to do that? 

 

George Dawson, MD, DFAPA

 

References:

1:  Pennisi E. Billions of North American birds have vanished. Science. 2019 Sep 20;365(6459):1228-1229. doi: 10.1126/science.365.6459.1228. PMID: 31604214.

2:  Rosenberg KV, Dokter AM, Blancher PJ, Sauer JR, Smith AC, Smith PA, Stanton JC, Panjabi A, Helft L, Parr M, Marra PP. Decline of the North American avifauna. Science. 2019 Oct 4;366(6461):120-124. doi: 10.1126/science.aaw1313. Epub 2019 Sep 19. PMID: 31604313.

3:  Loss SR, Will T, Marra PP. The impact of free-ranging domestic cats on wildlife of the United States. Nat Commun. 2013;4:1396. doi: 10.1038/ncomms2380. PMID: 23360987.

4:  Loss SR, Will T, Marra PP. Estimates of bird collision mortality at wind facilities in the contiguous United States. Biological Conservation. 2013 Dec 1;168:201-9.

5:  Ornelas-Eusebio E, García-Espinosa G, Laroucau K, Zanella G. Characterization of commercial poultry farms in Mexico: Towards a better understanding of biosecurity practices and antibiotic usage patterns. PLoS One. 2020 Dec 1;15(12):e0242354. doi: 10.1371/journal.pone.0242354. PMID: 33259478; PMCID: PMC7707464.

6:  CDC site on Avian Influenza (map of counties affected):  https://www.cdc.gov/bird-flu/situation-summary/data-map-commercial.html

7:  CDC site:  2020-2024 Highlights in the History of Avian Influenza (Bird Flu) Timeline. https://www.cdc.gov/bird-flu/avian-timeline/2020s.html

8: Barman S, Turner JCM, Hasan MK, Akhtar S, Jeevan T, Franks J, Walker D, Mukherjee N, Seiler P, Kercher L, McKenzie P, Webster RG, Feeroz MM, Webby RJ. Reassortment of newly emergent clade 2.3.4.4b A(H5N1) highly pathogenic avian influenza A viruses in Bangladesh. Emerg Microbes Infect. 2025 Dec;14(1):2432351. doi: 10.1080/22221751.2024.2432351. Epub 2024 Dec 9. PMID: 39584394; PMCID: PMC11632930.   

Details of the specific viral analysis for HPAI are included in this paper

 

Addendum:  I currently have an email in to Mexico's Secretariat of Agriculture and Rural Development (Secretaría de Agricultura y Desarrollo Rural) requesting more official numbers on the total numbers of domestic fowl euthanized due to HPAI since 2022. 

Graphic Credit:  From Wikimedia Commons.  Rollover photo or click to see full credit and CC license. This is the original unaltered photo.

Mouse-to-Mouse Resuscitation

 

A paper came out in Science 2 weeks ago (1) on the behavior of mice toward their unconscious or dead peers.  They have resuscitation-like behavior that consists of biting the face and tongue, clearing the airway, elevating the tongue of the unconscious mouse to revive them. Mice who were the recipients of this behavior recovered sooner than mice who did not receive these efforts.  The authors went on to see if they could localize the behavior in the brain and using modern neuroscience techniques, they able to show that they had localized the behavior to a brain substrate.  These papers have implications for psychiatry both at a theoretical and practical level.

In this experiment researchers used genetically identical mice (cross bred for 20 generations).  They followed their reactions closely across time epochs as they encountered a familiar partner anesthetized and unresponsive or euthanized (dead) mice. When compared with the active partner, mice spend 47.4% of the time interacting with the unresponsive partner compared to 5.8% of the time with the active partner.  They also displayed a specific pattern of behaviors directed facial area, trunk, limbs and head of the unresponsive partner. 31.8% of the time was directed at the orofacial area.  The overall duration of contact was extended with the unresponsive partner and it was more focused on the orofacial area.

To confirm the sequence of events, short acting (isoflurane) anesthesia was used to observe the partner response as the anesthetized mouse became less and then more responsive.  Time spent interacting with the anesthetized partner and the topology of interactions (more targeted orofacial activity correlated with the time anesthetized.  Deceased cagemates caused the same pattern of interaction but not sleeping cagemates because during sleep the directed behaviors led to movements of the sleeping mouse. This suggests that mice can differentiate responsive and unresponsive states in their partners.

The orofacial focused behaviors were studied under a high-speed camera.  It was discovered that in nonresponsive mice the tongue was bitten and pulled out of the mouth by casemates.  A similar tongue protrusion did not occur in unresponsive mice.  Pulling the tongue out resulted in a larger airway and the removal of foreign objects in the mouth. Placing the foreign object in a non-oral orifice did not result in removal. Stimulating the oral mucosa was also a strong stimulus for the righting response and arousal. 

Familiarity was a stronger stimulus for eliciting the grooming and resuscitation like behaviors than sex differences or similarities.  When given a choice between familiar partners – one anesthetized and one not – there was a preference for the anesthetized partner.  That did not persist when both target mice were unfamiliar.  The authors also demonstrated that the time spent with the unresponsive mouse did not decrease over a period of days – it did not show habituation.

After characterizing the unique behavioral aspects of the resuscitation like behavior the authors looked at the neural substrate. One hour after exposure to the unresponsive mice the cagemates were given 4-hydroxytamoxifen to label activated neurons.  Following 2 weeks of exposure several brain structures previously implicated in the observed behaviors including the medial amygdalar nucleus (MEA), paraventricular nucleus of the hypothalamus (PVH), basolateral amygdalar nucleus (BLA), hippocampus, and ventromedial hypothalamic nucleus (VMH) were examined. The number of tdTomato+ cells were noted in mice that had responded to unresponsive mice compared with controls (active partners).  This marker is a sign of the transcription factor c-fos and that neurons were recently active. Using a second set of probes roughly twice as many PVH oxytocin neurons were c-fos + and oxytocin + in the mice exposed to an unresponsive partner. 

An additional optogenetics experiment was done to look at the oxytocin PVH neurons.  Optogenetically silenced PVH neuron had the expected effect of reducing interaction time with the unresponsive partner. Optogenetically activating PVH neurons had the effect of increasing interaction time with an unresponsive stranger mouse.  An oxytocin receptor antagonist has the expected effect of reducing interaction time with the unresponsive mouse.

The authors conclude that they have demonstrated the necessity of both an oxytocin neuronal substrate and oxytocin signaling for very specific interactions and behaviors toward unresponsive mice.  Further, encountering a dead or anesthetized partner is required to elicit this response but it does not occur with a sleeping partner. They point out that rapid responses to an unresponsive partner can reduce the time it takes for recovery and decreases the risk of predation.  They suggest further work needs to be done on defining the neural network and sensory cues necessary for these behaviors.

As I read this paper I had a few thoughts:

1:  The hypothalamus is underemphasized in psychiatry.  We spent a couple of decades studying neuroendocrinology that was primarily focused on the pituitary gland. In clinical work, this is also an important system to be able to assess. But in much of the work about the theoretical basis of behavior – not much is said about the hypothalamus.  One example is the proximity of neurons underlying aggressive and sexual behavior in the lateral hypothalamus. 

2:  Social behavior versus the neurobiological substrate – psychosocial reductionists frequently treat the brain like a tabula rasa - not much is there until some kind of social learning or adverse event occurs.  In this case, adaptive complicated behavior is observed without any training.  The experiment illustrates both an anatomical and neurochemical basis for the behavior. Why would we expect anything to be different in humans?  And further - given the general case of biological diversity why wouldn't we expect this behavior to be absent in some and overdeveloped in others?  Even though the authors did not demonstrate this - why would we not expect that it could also be a learned behavior in individuals where it was not present or very robust?

3:  The measurements of activity in both the resuscitation-like and non-resuscitation behaviors were interesting.  Even though the overt behaviors were easily observed as occurring or not occurring – the neurons involved always had some level of activity. In other words – no target behavior did not equate to no neuronal activity.  It is not simply a case of networks being on or off. This has implications for how we attempt to correlate networks with behavior and the meaning of networks having a certain level of baseline activity.

All things considered; I thought this was a great paper. It reminded me of my biochemistry and pharmacology seminars in medical school where we would have spent a lot more time on the experimental methodology in this paper.  I did check my latest copy of The Molecular Biology of the Cell (7^th edition) and found that the discussion of optogenetics relative to this paper was very brief, but I suppose that makes sense.  From the standpoint of animal behavior this also recalls so-called altruistic behavior of some animals.  I have a file of that behavior observed in Humpback whales (Megaptera novaeangliae) interfering with killer whales (Orcinus orca) and hope to post something about that as well.

 

George Dawson, MD, DFAPA

 

References:

1:  Sun W, Zhang GW, Huang JJ, Tao C, Seo MB, Tao HW, Zhang LI. Reviving-like prosocial behavior in response to unconscious or dead conspecifics in rodents. Science. 2025 Feb 21;387(6736):eadq2677. doi: 10.1126/science.adq2677. Epub 2025 Feb 21. PMID: 39977514.

2:  DeNardo L, Luo L. Genetic strategies to access activated neurons. Curr Opin Neurobiol. 2017 Aug;45:121-129. doi: 10.1016/j.conb.2017.05.014. Epub 2017 May 31. PMID: 28577429; PMCID: PMC5810937.

Image Credit:

Generated by ChatGPT based on my parameters.  The original paper has a great image of the specific behaviors mentioned in this post. 

What happened to the Serotonin Hypothesis?

 

Biogenic amine hypotheses of depression date back 60 years at this point.  Ron Pies and I reviewed a couple of the key papers by Kety, Schildkraut and others that were some of the first to apply what was known about biogenic amine neurotransmitters to depression. These papers were elegantly written, keenly aware of the dangers of biological reductionism, and very clear that much more study needed to be done to either accept or reject the biogenic amine hypotheses.  Those hypotheses eventually extended to the specific neurotransmitters -  norepinephrine, serotonin, and dopamine.  Much has been written about the Chemical Imbalance Theory and more recently a Serotonin Theory of depression even though they do not exist.

I decided to study the transition in hypotheses over the course of my career by looking at major psychiatric diagnosis and counting the number of hypotheses in the literature for each diagnosis.  For the purpose of this post I will be posting a list of hypotheses about depression and discussing the implications. In general, there are many hypotheses about disorders that seem to linger in the literature. I have not found any solid evidence that hypotheses are accepted or rejected. There is also the possibility that they can be combined to produce new comprehensive hypotheses.  At this point I have not been able to identify any solid theories based on the development of hypotheses.  But before I get into that a brief discussion of definitions is in order to add some consistency to the rest of this essay. 

I will be using definitions from a book written in 1986 (1) because I think they are the clearest. The logical place to start is with a definition of a theory.  Theory is commonly mistaken for a hypothesis.  The best case in point that I can think of is the Serotonin Theory or Chemical Imbalance Theory.  By definition, a theory is a group of related principles that can explain and predict phenomenon in a restricted domain. The domain will vary according to the discipline. Medicine and psychiatry depend on empirical theories that in turn are proven or disproven based on observation and evidence. That demarcation extends to biology in general.  Examples of theories include Evolution, Thermodynamics, The Periodic Table in chemistry, and Germ Theory.  Any casual look at the biogenic amine hypotheses with respect to serotonin, norepinephrine, or dopamine will clearly show an elaboration of the neurochemistry and molecular biology of these systems. It will also show that the research is ongoing and that levels of prediction are not generalized enough for any marker to be used for prediction. At that level, biogenic amine theories do not exist and never have. There is additional confusion added by the common term conspiracy theories because in science they are really pseudo-theories and do not satisfy the general definition of a theory.  They provide false explanations and predictions.

Scientific laws explain how any branch of science organizes observations and explains them.  A good example would be the First, Second and Third laws of thermodynamics.  They are taught in physical science and engineering courses and do predict observations in physical systems at the macro level.  There are some specific laws in biology like mitochondrial DNA being inherited only from the mother and both parents contributing equal amounts of genes to offspring in sexual reproduction.

And finally, a hypothesis is a first step in developing laws and theories.  It consists of speculation about experimental observations at a more fundamental level.  The Serotonin Hypothesis for example was proposed since multiple observations about serotonin in depression were converging to suggest it played a central role in the disorder. It also occurred at a time when there was much active research on neurotransmitters and synaptic function. If it had been more widely accepted and there was a more comprehensive formulation that would have happened.  It did not and in at least one authoritative source – the American College of Neuropsychopharmacology – the Serotonin Hypothesis disappeared after the Fourth Generation of Progress in 1995.

I have included that transition in the four slides that follow.  I decided to include material from Goodwin and Jamison's Manic-Depressive Illness because it includes a commentary from the pathophysiology section of their book on bipolar disorder:

 

 

 

A comparison of dedicated chapters on serotonin between the 4th and 5th generations is also useful.  In the 4th generation there were 12 serotonin focused chapters and in the 5th there was one general chapter.

 As noted in the final summary of serotonin (last slide) , the research emphasis transitioned from strictly neurochemistry to the associated neurobiology and macro observations of brain networks.  At the same time current literature continues to emphasize the importance of serotonin systems in psychiatric disorders.  Although the ACNP Generation of Progress texts stopped with 5th edition I searched for evidence of the serotonin or any biogenic amine hypothesis in a recent comparable text (5).  There were no neurotransmitter centric mechanisms with a more primary focus on imaging receptors and transporter proteins and how neural circuitry was impacted.  Suggested mechanisms for depression converged on neurotrophic, immune, and neuroendocrine pathways (see table of contents below). 

While there has been no overt rejection of the serotonin hypothesis – people remain interested in it and it is useful to consider why.

1:  The search for the underlying pathophysiology of psychiatric disorders has continued emphasis.  The speculative mechanisms are broad and there are numerous hypotheses carried forward – much like the serotonin hypothesis. It seems unlikely that there will be a single basic mechanism leading to disorders based on the heterogeneity and polygenic nature of studied populations (see number of variants for major depression in the Polygenic Score (PGS) Catalogue.      

2:  Studying biological systems requires an appreciation of complexity – particularly when prediction is a dimension of theories. It is well known for example that biologically identical or nearly identical organisms can produce different physical and behavioral outcomes and until all of those mechanisms are appreciated and incorporated into hypotheses and theories – widely accepted overall theories are unlikely.

3:  There are imperfect classifications in biology, medicine, and psychiatry. One of the basic tenets in medicine is that no two people with the same diagnosis are alike.  There are obvious differences in biology, psychological and sociocultural factors.    

4:  Physical theories are not perfect.  There is active debate about theories that seem to be settled science and whether or not they are complete.   Many of those theories are predictive up to a point and useful for many applications - but deficient in some ways.  This is all part of the active process of science.

Despite these considerations – obvious questions about the serotonin hypothesis persist.   Why are medications with a high affinity for serotonin receptors and serotonin transporter (SERT) effective medications for several disorders?  Why in a recent preclinical study (6) was elevated extracellular serotonin  a common signal for several treatments – some of which did not target serotonin systems?  And – is it possible that serotonin signals are just the initial sequence of a larger series of events that leads to an antidepressant or anxiolytic response?

I would be remiss to not remind readers of the importance of analyzing the rhetoric in any scientific paper you are reading on psychiatric topics. On the issue of theories for example, my original source makes the following observation:

“What is a theory” is not as hard to answer as jesting Pilate’s “What is truth?”.  Indeed, one difficulty with our question is that there are so many accepted answers, not that there is none.  That is, the term theory is used in several distinct and legitimate ways in science and medicine, and an explanatory catalogue of those uses would fill many pages.  

“We will limit ourselves to the concept of a theory that suggests understanding, reliability, and grounded belief.” (p. 113)

If you find yourself suddenly reading about theories, hypotheses, or laws in psychiatry or any other branch of medicine look for the author's definitions of those terms.  Most textbooks in medicine and biology may mention brief definitions and references to thermodynamics and evolution but beyond that the terms are missing.  These terms are much more common in physical sciences where the studied objects are more easily classified and experimental observations are clearer.   

So what is the answer to "When did the serotonin hypothesis of depression disappear?"  One short answer is "between 1995 and 2002."  But the reality is that it is still with us despite active campaigns against it and several proclamations in the press that it is "dead".  At this rate it may outlive its detractors.

 

George Dawson, MD, DFAPA

 

References:

1:  Albert DA, Munson R, Resnick MD.  Reasoning in medicine: an introduction to clinical inference.  Baltimore, USA:  The Johns Hopkins University Press, 1988: 112-149.

2:  Pies R, Dawson G.  The Serotonin Fixation: Much Ado About Nothing New. Psychiatric Times. 2022 Aug 22

3:  Goodwin FK,  Jamison KR.  Manic-Depressive Illness.  New York: Oxford University Press, 1990. 

4:  Bloom, F.E. and Kupfer, DJ. Neuropsychopharmacology: The Fourth Generation of Progress. New York: Raven Press, 1995.

5:  Davis KL, Charney D, Coyle JT, Nemeroff C. (2002) Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia: Lippincott Williams & Wilkins, 2002.

6:  Charney DS, Gordon JA, Buxbaum JD, Picciotto MR, Binder EB, Nestler EJ.  Charney and Nestler's Neurobiology of Mental Illness.  New York: Oxford University Press, 2025.

7:  Witt CE, Mena S, Holmes J, Hersey M, Buchanan AM, Parke B, Saylor R, Honan LE, Berger SN, Lumbreras S, Nijhout FH, Reed MC, Best J, Fadel J, Schloss P, Lau T, Hashemi P. Serotonin is a common thread linking different classes of antidepressants. Cell Chem Biol. 2023 Dec 21;30(12):1557-1570.e6. doi: 10.1016/j.chembiol.2023.10.009. Epub 2023 Nov 21. PMID: 37992715.

Supplementary 1:  I contacted several experts involved in this research over the years.  So far none of the researchers I have contacted have responded to my questions that were specific to the serotonin hypothesis. 

Supplementary 2:  The book cover images and quotes are all property of their copyright owners and do not imply any connection to this blog. They are used here for illustrative and educational purposes. I encourage any readers of this blog to do their own research by reading the reference materials.  The ACNP 4th and 5th Generation of Progress are both available to read free online at the ACNP web site.

Should GLP-1 agonists be added to the drinking water?

For starters GLP-1 agonists are drugs like Ozempic and Weygovy.  See this post for a current list.  It is hard not to hear about them since they are heavily hyped in just about every form of media. They are being touted as a cure for just about everything.  Various celebrities are either promoting them or denying that a dramatic weight loss was associated with their use.  Some in the weight loss and exercise industry are pushing back with statements about side effects and rapid weight gain if you ever stop taking them.  The sales of these drugs is a windfall for the pharmaceutical industry and current pricing means that other businesses that make money from rationing access to medical care and medications will be trying to prevent their use.  I thought I would post a contrast today between the latest review of conditions these medications have been researched for and a new paper that suggests they may increase the frequency of psychiatric disorders.

The rest of the title comes from my experience in many medical settings over the decades.  Any time a medication is commonly prescribed you can count on someone saying “We should just put it in the drinking water.”  Examples over the years have been amoxicillin, H-2 blockers like ranitidine, statins, beta blockers, lorazepam, and even haloperidol.  It all depends on the prescription frequency in a particular setting. At the rate GLP-1 agonists have been hyped - somebody is saying it somewhere.  The irony in that statement is that many medications are now in the water supply and not doing anything for anybody.

When I describe this group of drugs as hyped that is exactly what I mean.  The only comparable hype has been for cannabis and psychedelics/hallucinogens.  Typical newspaper headlines about GLP-1s say they are wonder drugs and go on to describe them as indicated for several conditions ranging from addiction to Alzheimer’s disease.  Currently 5.4% of all medication prescriptions in the United States are for GLP-1 agonists.  These drugs have been around for 20 years and during that time transitioned from use primarily for Diabetes Mellitus Type 2 to weight loss. Despite all the clinical trials and experience with them I do not think the final verdict is in and the main papers relevant to this post will illustrate why.    

The first paper (1) is a large observational study using databases from the Veterans Administration (VA) health care system (1).  The authors describe the rationale of their study as looking at the real-world outcomes of the use of GLP-1 agonists – both the positive effects and adverse outcomes. They had an N of 1,955,135 followed for a median of 3.68 years looking at 175 health outcomes.  The authors use an interesting methodology.  Patients were recruited based on incident use of a medications for Type 2 diabetes mellitus (T2DM) between October 1, 2017 and December 31, 2023.  That created 4 groups based on the medical treatment of T2DM)  including GLP-1 agonists (N= 232,210), sulfonylureas (N= 247,146), Dipeptidyl peptidase-4 (DPP-4i) inhibitors (N= 225,116), and SGLT2i inhibitors (sodium-glucose cotransporter 2 inhibitors) (N= 429,172).  There was also a treatment as usual (TAU) group (N= 1,513,896) with Type 2 DM who took non-GLP-1 antihyperglycemics between the study dates of October 1, 2017 and December 31, 2023.  As a point of reference, I have included a table of the medications in each class used for T2DM. 

Glucagon-like peptide 1 (GLP-1) agonists	exenatide (Bydureon) exenatide (Byetta) liraglutide (Victoza) liraglutide (Saxenda) dulaglutide (Trulicity) semaglutide (Wegovey) semaglutide (Ozempic) semaglutide (Rybelsus) tirzepatide (Mounjaro) tirzepatide (Zepbound)
Sulfonylureas	Glipizide Glimepiride Glyburide
dipeptidyl peptidase 4 (DPP4) inhibitors	alogliptin (Nesina, Vipidia) sitagliptin (Januvia) saxagliptin (Onglyza) linagliptin (Tradjenta)
sodium−glucose cotransporter-2 (SGLT2) inhibitors)	bexagliflozin (Brenzavvy) canagliflozin (Invokana) dapagliflozin (Farxiga) empagliflozin (Jardiance) ertugliflozin (Steglatro)

 

This study was designed to assess groups on 175 health outcomes from these treatment cohorts compared with two control groups.  One control group was a composite of equal numbers of diabetic subjects using oral hypoglycemics and the other control groups was diabetics who continued GLP-1 agonists that they had already been started on.  Results varied but generally the health outcomes measured were significantly improved on the GLP-1 agonists compared with the controls and across categories.  For example, when GLP-1 agonists were compared with the sulfonylurea, DPP4, and SGLT2 classes outcomes were improved in 13.14%, 17.14%, and 11.43% of the outcomes respectively. 

Risk of adverse outcomes were 8%, 7.43%, and 16.57% in the same order.  Those adverse events in aggregate included: nausea and vomiting, gastroesophageal reflux disease (GERD), sleep disturbances, bone pain, abdominal pain, hypotension, headaches, nephrolithiasis, and anemia. 

When comparing the addition of GLP-1s to treatment as usual (the composite control) better outcomes were observed in 24% and increased risk of adverse outcomes in 10.86% of outcomes.

The reduced risk of several CNS disorders were estimated by hazard ratios and they were modestly decreased for alcohol use disorder, cannabis use disorder, stimulant use disorder, opioid use disorder, suicidal ideation of self-injury, bulimia, schizophrenia, seizures and neurocognitive disorders.  Risk reductions were in the 10-16% range. 

The authors of this paper use several graphing techniques to present their data.  They graphed hazard ratios for both improved and adverse outcomes and made negative log transformed Manhattan plots as a measure of statistical robustness as alternate graphing technique.  The paper is open access and I encourage reading the paper to see these data presentations.  I included a partial Forest plot at the top of this post to illustrate some of these graphs and the outcomes they measured. The blue dots indicate reduced risk relative to controls and the orange dots indicate increased risk (calculated as hazard ratios (3).

The strength of this study is that it summarizes a large amount of data across a VA database.  Since it is administrative data it is collected in nonstandard way and the diagnoses are not necessarily made by experts - this data may not be as robust as a prospective randomized clinical trial.  The population was older white veterans and that may be a factor when considering pleotropic effects.  The authors conclude that the GLP-1 agonists had broad pleotropic effects based on the spectrum of positive results and preclinical work.  They emphasize the positive results for neuropsychiatric diseases and disorders.  They discuss the issue of suicidal behavior and point out that earlier studies raised concerns to the point that the European Medicines Agency investigated and found no evidence for causality.  This study showed decreased suicidality and possible antidepressant effects.  The results generally showed significant positive effects on outcomes across major disease categories with a clear group of adverse effects.   

For comparison there is a recent large retrospective cohort study (2) that uses deidentified data on patients from 66 different health care organizations.  This appears to be a database with a commercial purpose, but I cannot identify what that purpose might be based on their web site.  In their rollover map, most of the deidentified patients in this database are Americans.  The study was approved by an IRB in China and I assume that is where the analysis takes place.  The study was focused on examining the effects of GLP-1 agonists on patients being treated for obesity.  Subjects were selected for a diagnosis of obesity and incident use of a GLP-1 agonist. It was a retrospective cohort analysis similar to the first study but propensity score matching was done to pair treatment subjects more closely with controls. Exclusion criteria included use of any other weight loss drug and any psychiatric diagnosis or significant symptom like suicidality.

The main results of this study are summarized in 3 tables in the body of the paper (Tables 2, 3, and 4).  Psychiatric outcomes were measured over a period of 5 years and the percentage of patients with major depression, any anxiety, any psychiatric disorder and suicidality (ideation or behaviors) we measured at 6 months, 1 year, 3 years, and 5 years.  The cumulative incidences of disorders and suicidality increased over these intervals.  Hazard ratios were calculated compared with the control population and they were generally doubled.  

Results stratified on demographic factors and GLP-1 agonist potency showed that both sexes had higher than expected psychiatric morbidity associated with GLP-1 agonist use but that women had significantly higher hazard ratios across all categories. Age was inversely correlated with older populations having lower risk of psychiatric comorbidity. Finally, the potency of the GLP-1 agonist directly correlated with potency of the GLP-1 agonist and time of exposure.  The authors discuss the limitations of their study and implications for future use and study.

Both studies generally illustrate some of the advantages and problems of conducting large clinical trials. The numbers in the hundreds of thousands or million plus range would be very difficult if not impossible to conduct randomized clinical trials on.  It is manageable using the naturalistic retrospective designs employed here commonly referred to as real world designs.  The obvious limiting factor is expense and the methodological problem of drop outs over time.  In these specific cases the first study is selecting a subject cohort based on a diagnosis of diabetes mellitus type 2 (DMT2) and the second obesity.  Both are heterogeneous populations with some overlap.  If I was influenced at all by some of the current psychiatric literature, I might suggest transdiagnostic features common to both but the importance of that term seems inflated relative to common medical diagnostic formulations.  Instead - I will use the parlance of medical trials and point out that there are signals in both papers.  Those signals are both good and not so good.  In the first paper there were clearly improvements in many medical outcomes when T2DM was treated with GLP-1 agonists in about 25% of the conditions studied and adverse outcomes in about 10%.  Improvement occurred in conditions outside of the endocrine/metabolic sphere including some psychiatric conditions. In the second study, significant increases in psychiatric conditions were noted to occur associated with GLP-1 agonist potency and total exposure in a population selected for obesity treatment.  The authors are careful to point out that obesity and metabolic syndrome may be a risk factor for mood disorders and they provide an excellent discussion of how trial design and patient selection may have affected these results.  

When these trials are reported in the news, they are generally not reported as showing modest results.  Side effects are typically ignored.  I have not heard anything about the study that showed that increased rather than decreased psychiatric morbidity may be a possible outcome.  The media generally reports them as miracle drugs and patients with the best possible results are given as examples.

GLP-1 agonists are clearly serious medications with potentially serious adverse effects.  The prescription of these medications requires close monitoring and thorough patient education.  If I was prescribing these medications today - in the informed consent discussion I would include the potential for modest outcomes, potentially increased psychiatric side effects, the general potential for side effects, and why outcomes may be variable.  I would also make sure to let people know that long term outcomes at this point are not known with any degree of certainty.    

   

George Dawson, MD, DFAPA

 

References:

1:  Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 Jan 20. doi: 10.1038/s41591-024-03412-w. Epub ahead of print. PMID: 39833406.

2:  Kornelius E, Huang JY, Lo SC, Huang CN, Yang YS. The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy. Sci Rep. 2024 Oct 18;14(1):24433. doi: 10.1038/s41598-024-75965-2. PMID: 39424950; PMCID: PMC11489776

3:  Spruance SL, Reid JE, Grace M, Samore M. Hazard ratio in clinical trials. Antimicrob Agents Chemother. 2004 Aug;48(8):2787-92. doi: 10.1128/AAC.48.8.2787-2792.2004. PMID: 15273082; PMCID: PMC478551.

4:  Sam AH, Salem V, Ghatei MA. Rimonabant: From RIO to Ban. J Obes. 2011;2011:432607. doi: 10.1155/2011/432607. Epub 2011 Jul 6. PMID: 21773005; PMCID: PMC3136184

Graphic credit:

Table at the top of the post of form Reference 1 and it is not copyrighted. The comparison Table was made by me.

Romantic Love and SSRIs

 

A paper came out this week that examined the relationship between selective serotonin reuptake inhibitors) SSRIs and romantic love. The lead author is a PhD candidate in anthropology with an interest in romantic love.  At first glance, the paper seems to run counter to a lot of sensational papers on the sexual side effects and possible persistent sexual side effects of SSRIs, because it found no differences between romantic love as assessed by a standardized scale and SSRI use. 

That is contrary to well-known sexual sides effects of these medications and the more recent controversy that SSRIs may cause persistent sexual dysfunction as either PSSD (Post SSRI Sexual Dysfunction) or PGAD (Persistent Genital Arousal Disorder). I have written about this controversy in the past and have not seen any useful advance in that literature.  Since that writing my information has been posted somewhere and I continue to get emails from people requesting my assistance in either assessing or treating PSSD.  I am no longer treating patients and therefore must decline. I am interested in researching this topic but do not have the resources on my own and my suggestions to various research entities have not produced any results.

This study looked at an N of 810 adults (48% women) from an original study of 1,556 adults from 33 countries who were defined as being in romantic love (Romantic Love Survey (RLS)).  The Passionate Love Scale (PLS-30) was used to identify romantic love.  The PLS-30 is a 30-point scale of descriptors of romantic love. Each item is rated on a scale of 1 (not true) to 9 (definitely true).  The scale is available at the above link.  This is an example of a typical item:

3. sometimes my body trembles with excitement at the sight of ____________

               not at all true 1 2 3 4 5 6 7 8 9 definitely true

 

By my inspection the 30 items of this scale are all cognitive and emotional features of love.  There are no items specific to sex or sexual fantasy.  The maximum scale score is 270 and participants in the RLS had to score a 130 or above and be in love for 23 months or less.  The authors of the scale suggest that a score of 106 -135 on the shortened version (15 items and a max score of 135) means – “Wildly, even recklessly, in love.”

The authors cite previous data suggesting the 2-year timeframe is necessary for romantic love and they removed 2 cases of high scorers because they were at the 4-year mark.  They deemed that 4 years of romantic love was improbable.

In their analysis the independent variable was SSRI use and they examined biological sex, mental health problems, intensity of romantic love, obsessive thinking, commitment, and frequency of sex as the dependent variables.  No specific details were given about the antidepressants – it was an SSRI or not binary.  At the time of the study only 9% of the sample (76 subjects out of 810) were taking SSRIs. Obsessive thinking was measured by a single question using a Likert rating.  Commitment was measured by adopting an item from another scale and changing the rating from 5 points to 9 points.  Frequency of sex was open to interpretation.  The question was “How often do you have sex on a weekly basis?” and a 50-point scale was used.  The mapping of responses to that scale is unclear from the description in this paper.  Mental health problems were measured with the Assessment of Quality of Life 4D (AQOL-4D) and distilled down to 1 question that looked at a anxiety, depression, or a combination ( “I do/do not feel anxious, worried or depressed). Any endorsement of these symptoms was considered a positive score of 1.

Binary logistic regression was done to see if any of the variables of interest predicted SSRI use and none was noted.  The authors confirm that none of their hypotheses about SSRI use correlating with less intense romantic love, less obsessive thinking, less commitment, and less frequency of sex were confirmed.  They conclude: “The results from this study demonstrate SSRIs use is not significantly associated with features of romantic love in our sample of young adults experiencing romantic love.”

I note that there was some reaction to this paper on social media.  Some were surprised by the results and some saw the result as a call for celebration. There are some people who claim that SSRIs have damaged their capacity for sex irreparably and the sexual side effects of the medication are well known.

The authors are more measured in their assessment of results. They comment on the discrepancy between their results and the literature on sexual side effects and consider several explanations.  The first has to do with selection bias.  Some people on SSRIs may have met exclusion criteria due to sexual side effects and for that reason would have been excluded from study.  Their demographic of young college age students may have been limiting. Is it possible that youthful vigor can counter known SSRI side effects? Specific drug, dosing and duration were also not specified.   

Any observational study like this one can be confounded by many factors.  As the authors mentioned selection bias can be primary. The original selection criteria may have selected out any persons with sexual dysfunction on or off SSRIs.  Interestingly the same phenomenon may occur in psychiatric practice.  Any psychiatrist who has been in practice for more than a few years has patients being seen on a long-term basis who are probably satisfied with treatment. Any medication being used may be well tolerated with few side effects.  Psychiatrists in that setting who routinely inquire about sexual side effects and relationship problems are not likely to hear about any.  The opposite selection bias occurs in some studies of these problems where subjects are recruited based on side effects.  In either scenario the true prevalence is likely to be over or underestimated.  

The authors advance several neurobiological explanations about brain substrates and serotonin that are highly speculative. Emotional blunting by antidepressants is discussed as a possible factor along with the potential brain substrates, but significant evidence against this occurring is not mentioned (3).   Several discuss the importance of the serotonin system and its up-regulation in romantic love.  Serotonin is a very important neurotransmitter in the human brain. Unfortunately, measuring it in vivo over time is very difficult.  Methods for accurate measurement in pre-clinical setting have only recently become available (5). One of the interesting findings is that serotonin can be increased in the extracellular space by several medications, therfore any serotonin-based mechanisms are not specific to SSRIs. I tried to capture the basic findings from this paper in the graphic at the top of this post.  The striking finding from Hashemi Lab is that antidepressants that purportedly have different up front mechanisms all increase extracellular serotonin. The discussion of serotonin is clouded by a lack of precision.  Terms like up regulated, down regulated, increase, and decrease are all meaningless unless it is relative to a specific location or structure and mechanism.   This finding needs to be incorporated into any discussion of how brain strictures are involved.  Any interested reader can find the referenced studies to see if that is happening.  In my experience it is not. 

In terms of the study design, metrics for anxiety, depression, and sexual side effects would provide additional comparisons.  Many psychopharmacological investigations use the Arizona Sexual Experience Scale (ASEX) to measure the sexual side effects of medications in a more detailed way.  The ASEX is a 5-item list that assesses sex drive, sexual arousal, erections/vaginal lubrication, orgasm ease and orgasm intensity using a 6-point scale.  It would also allow for the study of dissociations of romantic love from sexual behavior – as an example asexual adolescent crushes on one end of the spectrum and sexual behavior in the absence of romantic love on the other.  

In the end this study is reassuring that at least some people can take SSRI medications and it does not affect their love-life. But large questions linger at this point. The authors call for additional research. but it would also benefit from consultation with psychopharmacology researchers for additional design elements.  One interesting consideration is whether there is any dissociation of adverse effects between romantic love and sex and whether romantic love may be protective.  Like all complex human behavior precise mechanisms require more precise phenotypes and methodologies. 

Romantic love is no different.

 

George Dawson, MD, DFAPA

 

References:

1:  Bode A, Kowal M, Aghedu FC, Kavanagh PS. SSRI is not associated with the intensity of romantic love, obsessive thinking about a loved one, commitment, or sexual frequency in a sample of young adults experiencing romantic love. J Affect Disord. 2025 Jan 21:S0165-0327(25)00100-4. doi: 10.1016/j.jad.2025.01.103. Epub ahead of print. PMID: 39848471.

2:  Bode A, Kavanagh PS. Romantic Love and Behavioral Activation System Sensitivity to a Loved One. Behav Sci (Basel). 2023 Nov 10;13(11):921. doi: 10.3390/bs13110921. PMID: 37998668; PMCID: PMC10669312.

3:  Dawson G, Pies RW.  Antidepressants do not work by numbing emotions.  Psychiatric Times.  September 26, 2022.  https://www.psychiatrictimes.com/view/antidepressants-do-not-work-by-numbing-emotions

4:  McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, Manber R. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000 Jan-Mar;26(1):25-40. doi: 10.1080/009262300278623. PMID: 10693114.

5:  Witt CE, Mena S, Holmes J, Hersey M, Buchanan AM, Parke B, Saylor R, Honan LE, Berger SN, Lumbreras S, Nijhout FH, Reed MC, Best J, Fadel J, Schloss P, Lau T, Hashemi P.  Serotonin is a common thread linking different classes of antidepressants. Cell Chem Biol. 2023 Dec 21;30(12):1557-1570.e6. doi: 10.1016/j.chembiol.2023.10.009. Epub 2023 Nov 21. PMID: 37992715.5:  (Open Access)