Helen Flanders Dunbar, MD, PhD, recognized as the originator of psychosomatic medicine, was a clinician, writer, founder of the 

 As if that were not enough, she spent her professional life promoting the role of clergy in medicine and exploring accident proneness. Her work was also essential to the development of consultation liaison psychiatry.

 Her father was a mathematician, engineer, and patent attorney; her mother a genealogist; and her brother Francis earned an masters degree in botany at Stanford University. She too received a remarkable education At Bryn Mawr and Columbia she majored in mathematics and psychology. She then went on to earn 4 advanced degrees in 7 years. She attended the Yale Medical School in medicine and obstetrics. She wrote a doctoral thesis on Dante at Columbia University, while graduating magna cum laude from nearby Union Theological Seminary.

Her Episcopalian faith was a guiding light in her life, and she believed it should inform her medical practice. She worked closely with Anton Boisen, a clergyman inpatient at Westboro Mental Hospital, who was convinced that religion and psychiatry needed to be connected on a professional level. Together they trained ministers to work in medical settings.

In 1929, Dunbar broadened her medical and spiritual horizons by traveling to Europe. She met leading psychiatric figures of the day and visited Lourdes, the world’s most famous healing shrine in France, which had a profound spiritual effect.

She legally changed her name to Flanders Dunbar in 1938.

 It seems astonishing today that an accomplished woman had to change her name in an attempt to overcome the prevailing misogyny.

From 1930 to 1942, Dunbar was the medical director of the Council for Clinical Training of Theological Students and director of the Joint Committee on Religion and Medicine. During this time, she earned the soubriquet of “mother of holistic medicine” with her 1935 publication of 

Emotions and Bodily Changes: A Survey of Literature on Psychosomatic Interrelationships: 1910-1933

. In 1939, she became the first editor of the journal 

American psychosomatic medicine started in the 1930s. According to this school of thought, illnesses arose from the physiological effects of emotional stimuli. It was thought that certain psychodynamic patterns created typical illnesses, known as 

 Repressed (and forgotten) emotions emerged from the unconscious to target certain organs, producing psychosomatic disorders. Somatic dysfunctions thus arose from the patients’ emotional problems, which led practitioners of psychosomatic medicine to search for psychological profiles characteristic of specific syndromes. This expanded further to the belief that many diseases were psychogenic in origin and stressors, albeit undefined. Dunbar believed that having accidents was similar to the process by which other patients transformed psychological conflicts into somatic symptoms.

 Their personality styles and neuroses translated into 

After 1939, Dunbar gave up academic commitments, drank heavily, alienated followers, and left the American Psychosomatic Society. On August 22, 1959, the publication day of her landmark book 

“A magnetic, charismatic woman with a disturbed and beautiful soul and an almost magical gift of insight and intuition,” said her daughter Marcia Dunbar Soule.

It is difficult to put it any better, only to reflect that the passage of time may vindicate the views Dunbar held.

The Exceptional Brain and How it Changed the World

. He is Clinical Associate Professor at the Graduate School of Medicine, Wollongong University and Research Fellow, History Department, Stellenbosch University, South Africa.

He is writing a biography of Helen Flanders Dunbar.

1. Ozarin L. A psychiatric pioneer remembered

. March 3, 2006. Accessed February 16, 2021.

2. Kemp HV. Biography of Helen Flanders Dunbar (1902-1959). 

https://www.apadivisions.org/division-35/about/heritage/helen-dunbar-biography

4. Powell RC. Emotionally, soulfully, spiritually ‘free to think and act’: the Helen Flanders Dunbar (1902–59) memorial lecture on psychosomatic medicine and pastoral care. 

5. Marcia Dunbar-Soule Dobson. Quoted in Stokes GA Dunbar, Helen Flanders. In: Sicherman B, Green CH, eds. 

Notable American Women: The Modern Period

. Harvard University Press; 1980: 210-212.

Articles

The rise and fall of a brilliant medical pioneer. 

Helen Flanders Dunbar: The Mother of Psychosomatic Medicine

“A minute later she asked if I loved her. I told her it didn’t mean anything, but that I didn’t think so. She looked sad.”

It has been interesting to follow the patterns of leisure reading and television habits as the coronavirus disease 2019 (COVID-19) pandemic has unfolded. Initially and consistently throughout there has been interest in television series and movies with apocalyptic themes, particularly those in which destruction is wrought by viral disease. Movies bolstered by pseudo-science, such as “

,” have effectively mimicked the theater of pseudo-science that has defined 

 There have been the usual hordes of zombies, our commonest metaphor for virulent disease. Not unsurprisingly, there has been a parallel pattern in literature, including resurgent interest in the French-Algerian journalist and reluctant philosopher Albert Camus and his novels 

, published in 1947, describes a quarantine period in a coastal Algerian city suddenly beset by what appears to be bubonic plague.

 The government enforces a military lockdown on the city, and the story, narrated by a physician, follows the psychological impact of the enforced quarantine and the disease on a cast of diverse characters. The book, Camus’ longest work of fiction, is generally regarded as his masterpiece of absurdism. What is more absurd, after all, then the sudden appearance of a medieval disease, forced confinement—under the ironic penalty of death—with the dead and dying, and generally the catastrophic disruption of life as anyone heretofore has known it?

Camus, considered now among the founding figures of existentialism (a way of thinking defined by the subjective—the often unreasonable “I” as opposed to the objective voice of reason) consistently denied he was an existentialist at all, preferring the term 

. The existentialist can still find meaning in life; the absurdist generally cannot. This conclusion led to Camus’ most famous pronouncement that the only serious philosophic question remaining by the mid-20th century was whether to commit suicide or not.

, the issue of suicide plays out most fully in the character of Cottard. Cottard is an ill-defined criminal at the outset of the novel, whom we first meet as he attempts to hang himself in his apartment. He is fearful of arrest, but the coming of the disease and the lockdown gives Cottard a reprieve. He subsequently thrives as a black-market smuggler of cigarettes and alcohol. It is only with the imminent end of the disease and lifting of quarantine that Cottard disintegrates, becoming increasingly labile, eventually snapping on the day the quarantine is lifted, shooting random individuals and killing a dog before he is finally arrested.

, published in 1942 during the worst of the Nazi occupation of France, Camus paints a portrait of the sensual man, Mersault, who lives and works along the Algerian coast, utterly carefree, utterly self-absorbed. The book famously opens with the death of Mersault’s mother and his inability to feel anything for it as he attends her funeral. It is immediately clear that he lacks any depth of character. Lacking any moral compass, he allows himself to get involved in a friend’s bizarre revenge plot against his friend’s ex-girlfriend.

However, again ironically, Mersault soon finds himself incarcerated after he impulsively murders his friend’s ex-girlfriend’s brother during an odd exchange in which our protagonist, on his way to hide evidence, his friend’s gun, is accosted and attacked by the brother. In a state of sun-induced delirium, Mersault shoots his attacker. After a frenetic pause, Mersault then shoots the fallen man 4 more times.

What follows is Mersault’s trial, punctuated by character witnesses who all cannot wait to testify to how cold and unfeeling he is. It is clear that the authorities, given the situation, are willing to allow the killing as an act of self-defense, if Mersault will apologize. But he cannot. As he reflects, he cannot bring himself to feel any remorse or sadness over the murder. Nor can he bring himself to lie. He does gain some peace of mind during the night before his execution by accepting his fate as necessary to slake the bloodthirst of the crowd he will face in the morning. He is guillotined the next day.

“Don’t give way to conformity…stay lucid…But above all, in order to be, never try to seem.”

These words were written by Camus later in his short life (he died in a car crash at age 44). By then light-years removed from the life under Nazi occupation, with Madison Avenue and Hollywood having taken over the propaganda reins, his was now a cry for authenticity, a hearkening back to Mersault’s acceptance of his inability to be something he is not.

With the advent and distribution of multiple vaccines, the COVID-19 pandemic is, despite intermittent bursts of media hysteria, hopefully winding down. I can personally attest to dramatic and heroic moments throughout, but taking a view from on high—that is, the existential view—the lockdown and other restrictive measures meant to curb the virus will also lead to an 

 Death and debility from other diseases left untreated, explosive increases in substance abuse, depression, and anxiety, a growing pandemic now of pediatric mental illness (including children as young as 8 and 9 presenting with suicide attempts), acceleration of dementias, fracturing of relationships, the pervasive culture of internalized and externalized self-loathing ignited by restrictive measures over the course of a contentious election year, have all combined to make the actual viral 

death numbers shrink into the rearview mirror for some

, there is some hollow relief when the disease is declared contained, but the suffering brought about by the quarantine tempers any real joy. Cottard’s rage, transforming from internalized (his early suicidal gesture) to externalized (his shooting rampage) is 2020 in microcosm. Even more so is the example of Mersault in 

. COVID isolation has made strangers of us all, not least to ourselves. In my opinion, we are all at least a little more virtual than we were when this started, and the existential struggle to be rather than to seem is more difficult than ever.

Despite all of our own angst, the biggest existential lesson to take away at this historical moment is that we are responsible for our own resilience. Suffering is what it is. But anxiety symptoms is are a wakeup call, and depressive symptoms during the pandemic, really the reflecting on our own eventual demise, is not necessarily pathologic. Our patients are increasingly adrift; it is up to us to anchor ourselves, to value life amid death, to value relationships amid isolation, to avoid politicizing mental illness, and most importantly to be there for our patients.

director of Medical Psychiatry at the Newton-Wellesley Hospital in Newton, Massachusetts, and a clinical assistant professor of psychiatry at Tufts University School of Medicine in Boston.

2. Andrews TM. Sure, binge ‘Contagion’ and other pandemic movies right now. But their creators urge you to watch with caution. 

March 19, 2020. Accessed February 22, 2021. 

https://www.washingtonpost.com/arts-entertainment/2020/03/19/contagion-outbreak-stand-pandemic-movie-caution/

3. Jones V. Here are 8 books about pandemics to read in quarantine. 

. April 21, 2020. Accessed February 22, 2021. 

https://www.deseret.com/entertainment/2020/4/21/21216602/coronavirus-covid-19-books-pandemics-quarantine-what-to-read-the-plague-camus-the-stand-stephen-king/

. Trans. Thody P, O’Brien J. Marlowe & Co.; 1998.

7. Gorvett Z. Why most COVID-19 deaths won’t be from the virus. 

, May 28th, 2020. Accessed March 4, 2021. 

https://www.bbc.com/future/article/20200528-why-most-covid-19-deaths-wont-be-from-the-virus

8. Thankur R. Lockdowns Could Kill More than COVID-19. 

. June 12, 2020. Accessed March 4, 2021. 

https://www.internationalaffairs.org.au/australianoutlook/lockdowns-could-kill-more-people-than-covid-19/

9. Graham C. The human costs of the pandemic: Is it time to prioritize well-being? Brookings Institute. November 17th, 2020. Accessed March 4, 2021. 

https://www.brookings.edu/research/the-human-costs-of-the-pandemic-is-it-time-to-prioritize-well-being/

During the pandemic, Albert Camus’ existential novels have become newly popular—and with good reason. 

The Existential Fallout of COVID-19

In this conclusion of his miniseries on dementia, John J. Miller, MD, talks about keeping everyone safe when patients get violent, plus other nuances of care. 

is medical director, Brain Health, Exeter, NH; editor in chief,

; staff psychiatrist, Seacoast Mental Health Center, Exeter, NH; consulting psychiatrist, Exeter Hospital, Exeter, NH; consulting psychiatrist, Insight Meditation Society, Barre, MA.

Videos

Handling aggression in patients with dementia can be difficult...

Aggression in Patients With Dementia

found that a combinational pharmacogenetic test was a better predictor of medication blood level and patient outcomes than single-gene testing alone.

Common psychiatric medications for depression and anxiety can react with patients’ genes in ways that inhibit the drugs’ effectiveness. It is possible to test single genes for potential interactions, but Myriad Genetics has developed a test that 

 The study found that testing variations in multiple genes led to better, more predictive results.

The study’s lead author was Anthony J. Rothschild, MD, Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. In the article, he and his coauthors explained the importance of the findings as follows: “This evaluation of clinical validity shows that only the combinational pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”

The study was based on data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial.

 Between 2014 and 2017, the GUIDED trial drew participants from 60 psychiatry and primary care centers around the United States. In order to be eligible, participants needed a major depression disorder diagnosis and a score of 11 or more on the 16-item Quick Inventory of Depressive Symptomatology Scale at screening. They also needed at least 1 failed trial of psychotropic medication during their current depressive episodes.

 Participants were placed blindly into the pharmacogenomic-guided care or conventional treatment arms of the trial for 8 weeks. The researchers then measured and analyzed their outcomes.

The GUIDED trial did have some limitations. It was not a controlled pharmacokinetics study, meaning “blood levels were not controlled for time of intake or medication adherence.”

 As blood levels were only collected at screening, they could not be directly linked to adverse events or other outcomes. Still, the results were promising.

“This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing,” Mark Pollack, MD, chief medical officer of Myriad Neuroscience, said in a statement to the press. “Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.”

1. Rothschild AJ, Parikh SV, Hain D, et al. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. 

2. GeneSight psychotropic test’s combinational approach proves better than single-gene testing at predicting patient outcomes and medication blood levels. 

February 8, 2021. Accessed March 4, 2021. 

https://www.globenewswire.com/news-release/2021/02/08/2171246/0/en/GeneSight-Psychotropic-Test-s-Combinatorial-Approach-Proves-Better-than-Single-Gene-Testing-at-Predicting-Patient-Outcomes-and-Medication-Blood-Levels.html

A study finds that testing genetic variations can predict outcomes and medication blood levels in patients with depression. 

How Will Patients React to Medications? The Answer May Be in Their Genes

Decades of anhedonic remission soothes the writer’s soul.
Perduring core muscles sing hallelujah to a once despondent hole.

Seasons of academic debacle rummage for serotonergic boost.
Providential intervention reveals the antidote for parched roots.

Periods of deflated ego lament authentic loss.
Hospitable hands offer a resurgence during a wilderness inundated with wistful moss.

Times of poetic creativity deliver an affordable prescription for the 1 in 5.
A divine gift provides the mollifying balm for the author to thrive.

Share feedback with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

 is clinical assistant professor at the University of South Carolina School of Medicine-Greenville and medical director & division chief for Adult Inpatient and Consult-Liaison Services for the Department of Psychiatry and Behavioral Medicine at Prisma Health-Upstate. He currently serves on the APA Task Force to Address Structural Racism Throughout Psychiatry as well as the Diversity & Inclusion Section Editor and Advisory Board member for 

Catharsis expressed in a pen, it was a tool to get through the hard times, even medical school.

Bard Self Disclosure

Richard Berlin, MD, shares poetry from James Crews, evokingm imagery of the cold weather. The full poem can be found 

has been writing a poem about his experience of being a doctor every month for the past 23 years in

in a column called “Poetry of the Times.” He is instructor in psychiatry, University of Massachusetts Medical School, Worcester, MA.

"...remember this one life is a gift each of us was handed and told to open..."



Cloudy Eyes, Chapped Lips, Icy Air

 has been writing a poem about his experience of being a doctor every month for the past 23 years in

 in a column called “Poetry of the Times.” He is instructor in psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts. 

to twilight, Freud’s bust, the graybeard

But his head is nodding Yes, and I talk—

I loved, books that kidnapped my attention,

and the helpless feeling I’d become a doctor

and still couldn’t save him, the professor

the flash of insight: training had begun.❒

My life pasted on his wall to analyze, a flash of insight came to me: Training had begun.

Psychiatric Residency Interview

Conversations in Critical Psychiatry is an interview series that explores critical and philosophical perspectives in psychiatry and engages with prominent commentators within and outside the profession who have made meaningful criticisms of the status quo.

 is the Theodore J. Castele Professor of the History of Medicine and Associate Director of the Program in Medicine, Society, and Culture at Case Western Reserve University, Cleveland, Ohio. He holds secondary appointments in the Departments of Bioethics and Psychiatry. He earned degrees in history from Wesleyan (BA), Stanford (MA), and Johns Hopkins University (PhD); he also studied psychiatric epidemiology at Columbia University. He is the author of 

Imperial Bedlam: Institutions of Madness and Colonialism in Southwest Nigeria

 (University of California Press; 1999); 

Electroconvulsive Therapy in America: The Anatomy of a Medical Controversy

 (Polity Books; 2020). His articles have appeared in journals including the

 Journal of the History of Medicine and Allied Sciences, Harvard Review of Psychiatry, Bulletin of the History of Medicine

Dr Sadowsky is a leading historian of psychiatry, and one I am proud to call him my teacher. As a psychiatry resident, I attended his lectures on history of psychiatry as part of our residency didactics and benefitted greatly from them. Sadowsky was 

 in 2017 by Greg Eghigian, PhD, about his book, 

, an interview that is well worth revisiting. The present interview is about his new book 

. I admire Sadowsky for his ability to tackle complex and controversial issues with scholarly rigor and fair-minded appraisal, and I am delighted to have him participate in this series.

 Before I jump into my questions, I want to give you an opportunity to introduce your book to the readers on your own terms. What are the issues that occupy you? I suppose some folks on hearing about 

 may reflexively think, “What… another book about depression? Don’t we have enough of those already?” Perhaps in your response you can also touch on why a new history of depression was needed in your opinion.

 First, not many of the books about depression are histories. Take 

The Noonday Demon: An Atlas of Depression

 I think it is great, but it only has a single chapter on history, and it is a brief account. With a few exceptions, most of the history books are focused on antidepressants, and many other treatments have important histories—psychodynamic psychotherapy, cognitive behavioral therapy (CBT),electroconvulsive therapy (ECT), and the many approaches that preceded the 20th century, for example.

A couple of long, detailed histories of depression barely mention ECT. This is weird. I know opinions about ECT are divided—

 is also a book about controversy—but whatever you think about ECT, many psychiatrists consider it among the best treatments psychiatry has for serious affective disorder. Imagine for a moment a historian of medicine in another specialty writing a long history of a particular ailment and skipping briefly over a treatment many doctors say is among the most effective! Previous histories of depression have also been a bit weak on psychoanalysis, which is a strong interest of mine.

Second, little existing historiography of depression focused on patient experiences and self-representations. This is not an easy area to research, because a lot of depression treatment takes place in private office practice, a confidential setting, and little documentation is publicly available. I would have liked to do more, but I hope I pushed the field a little in that direction. But I want to add immediately that some historical and other critical studies of psychiatry see patient voices as only a way to criticize psychiatry. It is important to document patient complaints, but some critics of psychiatry go to tortuous lengths to deny any therapeutic benefits. Honoring patient voices also means seeing that many feel helped by treatment.

I also wanted to draw attention to the politics of inequality. Like so many other illnesses, depression hits different populations to different extents. Solomon did draw attention to this, but most of the historical work on depression restricts inquiry to the gender ratio, which is an important axis, but not the only one. Class, race, and LGBT status, for example, also matter for depression, and I hope future historians will develop this further.

Finally, I wanted to make the story more global, less focused entirely on the West and especially the United States, though I do give the US a lot of attention. Anthropologists and global mental health workers have looked at the wider world, but historians really have not, not for depression. I would like to have gone further here, too, and I hope others will.

 What I love about your book is that it does not settle for easy answers. It embraces the uncertainty, ambiguity, contradictions, and flux inherent in the very subject matter. One of the difficulties with studying depression is it is a fluid entity with variations across both time and space. Is depression the same today as it was in the 17th century when Robert Burton wrote 

? Is depression the same thing in the United States and Nigeria? These are obviously thorny issues. Can you elaborate on the approach you take to address this? How can we tell a coherent history of something if we are having a hard time pinning down what that “something” is?

 The various illness categories—or, as it may be in some contexts, conceptions that are not illness categories—are already included in a long running discussion of the comparability of diagnostic categories and sickness experience across time and space. The discussion is a story itself.

Most of the illness states I compare have a core feature, which is excessive sadness or blue mood, in whatever that particular context considers excessive. But some definitions of depressive illness consider this a common, but not necessary, feature for diagnosis. As you know, major depressive disorder (MDD) in DSM-5 does not require depressed mood as a necessary criterion, provided there is loss of interest and 4 other symptoms. I draw (lightly) on Ludwig Wittgenstein, PhD’s concept of “family resemblances.”

 Things do not need precise overlaps to have similarities that justify comparison. For all the imperfections of the DSM, I think if you look at the menu of symptoms for MDD, they do form a constellation of related signs of suffering that have been clumped together in disparate contexts.

Over-emphasizing cultural differences has its own risks. I show in chapter 1 that the idea that African societies had little or no depression had roots in some frankly racist ideas. Universalizing labels can be a form of cultural imperialism, but over-insistence on difference forecloses possibilities for meaningful comparisons. And some who think depression is a purely modern or Western illness might be surprised at how many cultures, across time and space, have had some conception of excessive sadness as a malady.

Chiara Thumiger, PhD, a great historian of madness in antiquity with whom I am collaborating on a new project, set forth 4 principles for comparisons across time and space

1) The human mind is biological, a part of a shared evolutionary heritage, so you can expect some measure of universality;

2) the mind and mental life are not confined to the brain, but involve other parts of the body;

3) mind and brain are situated in and shaped by culture, so universality will always be limited; and;

4) every individual has an irreducible quality, uniqueness. I think these are great principles to keep in mind.

 It is apparent from your book that one cannot even begin to do justice to the history of depression if one is not willing to tackle the anthropology, literature, phenomenology, philosophy, science, and sociology of depression. Despite the demands, you really do quite a remarkable job of drawing on these diverse fields to piece together the history. In the course of writing this book, did you suffer from a sort of identity crisis at any point, along the lines of, “Am I even writing history anymore?”

 Making sense of anything for me starts with chronology and making rough periodizations. But, as you say, depression demands multiple perspectives. I did sometimes think I was straying from my disciplinary home. But who cares? My goal was to illuminate my subject, not to show loyalty to my discipline.

I have known some academics who are oddly certain that their own discipline provides the ultimate answers. Not me. I consider history a good lens among many, and I am still learning much about the others. I look forward to you and others helping me learn more philosophy.

 You are clearly dissatisfied with a lot of popular critiques of depression. You write, “One thing this book is not is a long lament on the over-diagnosis of depression, and the turning of life’s normal suffering into a medical problem.” Tell us more about your dissatisfaction with this line of criticism.

 Many individuals look at the high numbers of individuals with a depression diagnosis compared to previous times and take it as self-evident that we are over-diagnosing. It is not. Rising diagnosis rates is a valid reason to be concerned about over-diagnosis, but it is not proof. In 1950, much of psychiatry was concerned that we were under-diagnosing depression, so from that perspective, we may be finding a lot that we had been missing. We should at least consider the upside: More diagnosis means that more individuals who could use professional help are getting it.

As for medicating the normal pain of living, we should keep in mind that getting treatment for depression, whether in psychotherapy or with antidepressants, does not protect anyone from suffering, though one hopes it is reduced. Life remains hard. And many patients with depression welcome sadness as a relief from feelings of deadness or numbness inside.

I do offer some defense of antidepressants against their most severe critics in the book. But I also think we are probably over-reliant on them. I think the benefits of psychotherapy, particularly long-term insight-oriented therapy, have become underrated in the antidepressant era.

Still, why some advocates of psychotherapy are so adamantly and categorically opposed to any medication use, or to any suggestion of a biological component to depression, is a mystery to me. I have read many hardline critiques of biological and pharmaceutical psychiatry that are focused on whether the evidence for efficacy is robust, or questioning the philosophical underpinnings of the enterprise, or worried about adverse effects, or indicting the pharmaceutical industry. The thoughtful challenges have reinforced my view that we are over-reliant on drugs, at least for some populations. Other critiques have struck me as dogma masquerading as critique. But even the smartest of them have not convinced me that antidepressants are worthless, a claim several important voices have made.

The biology of depression is incompletely known, and much of it may remain permanently elusive. But the idea that depression is purely psychological is, I think, implausible. But so is the view that depression is purely biological. The dichotomy itself is the problem. Mark Solms, PhD, says that mind and brain are 2 ways of looking at the same thing. I find this more helpful. I do not understand how something could affect either the mind or the brain independently of the other. That is not a coherent idea.

I am getting away from your question a little, but it is an important point. Proponents of a life history emphasis in etiology sometimes take it as self-evident that if trauma or neglect is the cause, the better solution must be psychotherapeutic, as opposed to somatic. Psychotherapy might be the better treatment, but it is not self-evident just from the etiology. And the reverse: individuals who lean towards more organic theories of etiology—genes, brain chemistry—sometimes take it as self-evident that the better solution must be something more physical, like a drug or ECT. Again, this could be true, but it is far from self-evident. In any event, I think monocausal approaches to etiology are misguided.

 You write at one point, “The growing interest in depression led more people, both professional and lay, to learn to label problems as depression, which was a growing idiom of distress before the advent of antidepressants . . . The medications, though, provided new incentives for multiple actors—pharmaceutical companies, doctors, patients, and patient’s families—to identify cases of depression” (page 98).

I suspect you would have been writing a very different history of depression if antidepressant medications had not been developed or if their use had continued to be severely restricted due to tolerability. A curious thing though is that anxiety disorders are more common in the general community than depressive disorders, and antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are not just antidepressants but also antianxiety medications. We could perhaps imagine an alternative history in which anxiety was the idiom of distress, SSRIs had been marketed as antianxiety rather than antidepressant, and you would perhaps be writing a book about the empire of anxiety, and the continuous historical links between melancholia and anxiety! Is it merely an accident of history that we ended up in the age of depression rather than the age of anxiety?

Cross-cultural study has shown that the separation of anxiety and depression is a convention of Western psychiatry (which is rapidly becoming a global or cosmopolitan psychiatry, with both good and bad effects). Many healing systems around the world assume anxiety and depression are aspects of a single thing. And even in the West, the separation is somewhat new, a Kraepelinian innovation.

You present an interesting counter-history. I am not sure the trajectory has been solely drug-driven, though. When the monoamine oxidase inhibitors and tricyclics were developed, psychiatrists were looking for depression treatments, and had been for decades. That is part of why these drugs came to be called antidepressants.

One curious thing though is that important anxiety medications and antidepressants were introduced around the same time, and yet from a broad cultural point of view, we had first an age of anxiety, the immediate postwar period, followed by an age of depression, starting sometime in the 1970s and becoming more visible in the 1980s. In what I consider the most speculative portion of my book, I try to understand that as possibly representing wider cultural moods, perhaps rooted in different forms of capitalism. As speculative as that section is, I included it because I thought it was worth thinking about.

 One thing I had not quite appreciated before reading your book was that the psychoanalysts were quite sympathetic to the notion of gene-environment interactions when it came to depression (the genetic factors being described in the language of their day as a constitutional factor or inborn tendency). It is rather unfortunate that we have this caricature of psychoanalysts in contemporary consciousness as psychological reductionists and dismissive of biology.

 I have long thought that psychoanalytic hostility to biology was a caricature created by the critics of psychoanalysis—I wrote an article about it in 2006

—but I was surprised by how right I was in the case of depression. The psychoanalysts who denied any role of biology in causing or treating depressive illness were defying the views of the most prominent theorists, including Freud; Karl Abraham, PhD; Otto Fenichel, MD; Edith Jacobson, MD; John Bowlby; MD; Silvano Arieti, MD; Julia Kristeva, PhD; Nancy McWilliams, PhD, ABPP; and Otto Kernberg, MD, FAPA. I am naming names here because they are so prominent, and they wrote such widely read books.

 You do not spend much time on the creation of MDD as a diagnosis in DSM-III (and the surrounding politics of it). I wonder how different future course of events would have been in the absence of such a diagnostic category. If you look at DSM-II, depression was fragmented across many different sections under many different diagnoses. We had diagnoses in DSM-II such as “involutional melancholia,” “manic-depressive illness, depressed type,” “psychotic depressive reaction,” “depressive neurosis,” and “neurasthenic neurosis.” I suspect that this DSM-II organization of depression would not have been particularly conducive to the process of empire-building!

 That is a great question, and I could have given this change more attention in my discussion of the DSM. But I wonder if the creation of the category (if not the precise name) of “Major Depressive Disorder” was already in process before DSM-III, reflecting the growing research interest in depressive illness in the years preceding the revision of the manual.

 As a psychiatrist, when I look back at the evolution of depression, a pair of developments in recent decades appear to me to be notable, although their historical significance is probably yet to be seen. The first is the notion of treatment-resistant depression (TRD). There has been increasing recognition that a majority of patients either do not experience resolution of their depression with standard antidepressants, or if do, they do not stay well over time. This has led to more aggressive pharmacotherapy, such as augmenting with atypical antipsychotics, and the recently approved medication esketamine. The second is that bipolar disorder has been steadily encroaching on the territory of depression, such that even in the absence of mania or hypomania, many psychiatrists classify the presentation as being on the bipolar spectrum. Just as the development of antidepressants led to an increase in the diagnoses of depression, development of medications for bipolar depression have led to an increase in the diagnoses of bipolar disorder. Any preliminary thoughts of these developments as a historian?

 It is of course awful that some depressions are so hard to treat. I am not a clinician, but I wonder if many of those that seem resistant to aggressive medication treatment might respond to intensive psychotherapy, which can be expensive, or to ECT, which has risks of adverse effects (risks which are, in my opinion, generally greater than the risks of antidepressants, though I think in some cases, the risks may be worth it). As a historian though, I would ask if the whole category of TRD does not represent some progress, since it implies the other kind. A 19th century alienist could not do much about any severe depressions at all. Many of my colleagues in history of medicine, and especially history of psychiatry, get nervous at any hint of a progress narrative, but I do not mind saying I think we have a better repertoire of treatments for depressive illness now than we did in 1850. All the treatments have downsides, but that is true of medical treatments in general.

I am aware of the rise of bipolar diagnosis, but I have not followed it closely. From a practical point of view, of course, what matters about a label is matching the individual in pain to the best treatment possible, and that is a clinical question. My historian’s take is: The safest prediction is that changes in diagnostic fashions are going to keep happening, and they will not necessarily be driven by genuine scientific advance. The whole enterprise is not worthless, but we should not assume the present trend represents the final or best word. On this point, I do worry about progress narratives.

 Your admiration for Adolf Meyer, MD’s, approach is obvious in your book. At one point you write, “The product they [the patients] want resembles the one Meyer was selling, though it is hard to find in the current market” (p 163).

 The assessment of some of your colleagues has been rather harsh in comparison. Edward Shorter, PhD, in 

 described him Meyer as (unfairly I think) a “second-rate thinker . . . [who was unable] to disentangle schools that were absolutely incompatible, and ended up embracing whatever new came along.”

, is also rather unkind in his assessment, saying that Meyer’s success had “little to do with nosology or therapeutics and everything to do with marketing.”

 Perhaps you would like to set the record straight here regarding Meyer?

First of all, a confession: Meyer bores me. I do not find him an exciting thinker. Second, some of the criticism of Meyer has merit. Greenberg has a point Meyer probably did not advance diagnosis or therapeutics much, at least not in a systematic way that could be passed down. To be fair, though, much progress in psychiatric therapeutics has been somewhat accidental. ECT therapy was based on a hypothesis—an alleged antagonism between schizophrenia and epilepsy—that is no longer considered likely, and schizophrenia is not now the main indication for ECT anyway. A lot of psychopharmaceutical development came from chance observations of the effects of drugs that were being tried for other purposes.

The reason I want to give Meyer some credit is his rejection of reductionism. He wanted clinicians to see patients as biological organisms, with a particular life history and psychology, and a social context. This should be what we all want now. If Meyer was such an effective marketer, why has there been so much reductionism?

 In a very memorable passage of your most recent book, you compare history with psychoanalysis: “One theory about how psychotherapy works is that patients are locked into repeatedly telling the same story about themselves – about their loneliness, or their victimization, for example. The therapy helps patients see that they do not have to repeat the same story. They can tell new stories of their lives. History can have a similar role . . . We do not have to live the same story, time after time” (page 133).

 Later in the epilogue you again refer to the study of history as a means of guarding against compulsive repetition. Can you summarize here what history tells us we can do differently going forward when it comes to our understanding and treatment of depression?

 I will name 2 things. First, we do not need to keep having the same arguments about whether depression is fundamentally biological, or really the result of trauma in life, or the result of social forces. I fear that we will, because of the tenacity with which some individuals hold to the insistence that we must choose. It is my hope that by showing historically how insistence on a single approach leads to dead ends, we might be liberated from this. In the epilogue, I used the image of a quarreling couple, stuck in the same fights for decades on end. A good marriage counselor might be able to remind each partner that the other has things to offer.

I also hope we might be liberated from the cycle of hype and disappointment about new treatments. Most of the major treatments for depression over the last century (psychoanalysis, ECT, CBT, and antidepressants) have been overemphasized by some zealous proponents. Then disappointment (dare I say, depression?) comes when the harms or limitations of the treatments become clear. In turn, we rush to condemn the old treatment as worthless and latch on to something new, which is thought to lack the flaws of the earlier ones. But the old treatments still had something to offer, and the new ones prove to have flaws, though we may not see them right away.

New treatments are going to come, as they should. When they do, let us try not to overdo the hype, the radical rejection of the old ones, or the disappointment in the new that follows. In addition to helping patients overcome repetitions, psychotherapy can help patients to see individuals in and things in their complexity. Sometimes we, as professionals or as whole societies, can act like an individual searching for love, and finding partners we initially idealize, only to come to despise them when they inevitably disappoint us. We would do better to tolerate ambiguity. I hope 

The opinions expressed in the interviews are those of the participants and do not necessarily reflect the opinions of 

is a psychiatrist in Cleveland, Ohio, and clinical assistant professor of Psychiatry at Case Western Reserve University. He is a member of the executive council of Association for the Advancement of Philosophy and Psychiatry and has been actively involved in initiatives to educate psychiatrists and trainees on the intersection of philosophy and psychiatry. He is also a member of the 

Dr Aftab and Dr Sadowsky have no relevant financial disclosures or conflicts of interest.

A History of the Mind and Mental Health in Classical Greek Medical Thought

5. Sadowsky J. Beyond the metaphor of the pendulum: electroconvulsive therapy, psychoanalysis, and the styles of American psychiatry. 

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 has published the encouraging results of Karuna Therapeutics’ EMERGENT-1 phase 2 clinical trial for their novel treatment, KarXT. A proprietary oral modulator of muscarinic cholinergic receptors, KarXT offers a new approach to treating patients with schizophrenia.

, Steve Brannan, MD, chief medical officer of Karuna Therapeutics and lead author of the manuscript, had this to say: “The findings published in the 

 from the EMERGENT-1 Phase 2 trial further support the potential impact we believe KarXT can have on addressing schizophrenia with a new mechanism of action to effectively treat the condition, while lessening the concerning side effects seen in the current standard of care. Overall, we are encouraged by the data generated to-date and look forward to continuing to progress the EMERGENT clinical program through Phase 3 studies.”

Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia

 The EMERGENT-1 phase 2 trial lasted 5 weeks and enrolled 182 adults with an acute exacerbation of schizophrenia. Treatment with a twice-daily, flexible-dose of KarXT demonstrated a statistically significant and clinically meaningful 11.6-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo at week 5.



Additionally, 4 of the 5 prespecified secondary outcome measures showed statistically significant reductions for the KarXT group compared to placebo at Week 5. These secondary outcome measures included PANSS positive symptom subscore, PANSS negative symptom subscore, PANSS Marder negative symptom subscore, and Clinical Global Impression – Severity frequency counts.

“Many people living with schizophrenia have persistent symptoms, experience poor quality of life and impaired ability to function, despite treatment with current antipsychotic drugs,” said Jeffrey Lieberman, MD, professor and chairman of the department of psychiatry at Columbia University, and coauthor of the manuscript. “The clinical trial results with KarXT highlight its potential to be a differentiated treatment option with a completely new mechanism of action for people living with schizophrenia, offering relief from acute psychotic symptoms without the debilitating side effects associated with the current standard of care.”

KarXT was generally well-tolerated, with the most common adverse events being constipation, nausea, dry mouth, dyspepsia and vomiting, though all were mild-to-moderate in severity and were not associated with treatment discontinuation. Rates of nausea, vomiting, and dry mouth decreased over the course of the trial, while rates of constipation remained constant. Both the placebo and KarXT treatment groups showed incidences of somnolence, weight gain, and extrapyramidal symptoms, which are common problematic side effects of current antipsychotic therapies.

“These findings support the potential for KarXT to treat symptoms of psychosis in schizophrenia without producing the common problematic side effects of current therapies, such as weight gain and extrapyramidal symptoms. Given these encouraging results, we have advanced KarXT into Phase 3 clinical development in our efforts to provide a meaningful, new, non-dopaminergic treatment option for this serious neuropsychiatric disorder affecting more than 21 million people worldwide,” Brannan said further.

1. Brannan SK, Sawchak S, Miller AC, et al. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2017015

The chief medical officer of Karuna shares his thoughts exclusively with Psychiatric Times.  

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