crafting a portrait of a Medico della Peste,

to drown the stench, his waxed black cloak

they worshipped. And I wonder if today’s

and robe, would the Inquisition have seen

he held out to the world like an offering?

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.

Articles

"While I watch the artist paint, I imagine him in the time of plague..."

Modern Medieval Artist

is professor of psychiatry and the Former Von Tauber Chair,

Psychiatry & Behavioral Sciences at Nassau University Medical Center.

My wife and I sat down to watch the news on a pleasant summer evening in 2020. That day’s contents included reports about multiple deadly hurricanes in the Gulf of Mexico, wildfires in California, and racial riots in big and small cities across the United States. Simultaneously, the world dealt with the COVID-19 pandemic that had killed 1.3 million individiuals worldwide and 230,000 in the United States, as of November 2020.

Signs of the devastation wrought by the pandemic were ubiquitous. Hospitals were overflowing with severely ill patients, and the staff had to use temporary morgues in huge, refrigerated trucks. Consequently, there was a higher incidence of physical and psychiatric illnesses, even in those not infected by the virus. Millions lost their jobs, and there was no end in sight to this agony. Quite fortuitously, our 20-month-old granddaughter came to our rescue with her intelligence, loveliness, curiosity, and guilelessness.

Before describing how a toddler living 1000 miles away can salvage her grandparents’ sagging spirits, let me provide the context. My wife, a computer professional, and I, a psychiatrist, became empty-nesters when our daughter left home to study medicine this past summer. In choosing medicine as her career, our daughter followed her physician brother’s footsteps. Our son is married to his classmate in college, also a physician, and the couple has a lovely 20-month-old daughter, Mia. Mia is a beautiful baby with chubby cheeks, large eyes, an expressive face, and a full head covered with unruly, curly, dark hair. She is very curious about the world around her. Mia loves the outdoors and often asks her parents to take her to their backyard, where she runs around with boundless energy. Nothing escapes her attention, whether it be an airplane flying in the distant sky, a helicopter hovering low nearby, or beautiful birds sitting on tree branches.

Mia is a ray of sunshine in an otherwise bleak current environment. Her parents call us several times a week. Our son and daughter-in-law live in Nashville, TN, and we live on Long Island, NY, making video chats via phone/computer the only link between us. We are grateful for these video chats in our lives because they offer us such an enriching experience.

While watching the news on that late summer evening, the phone rang with FaceTime’s familiar sound. Momentarily, we saw Mia seated in a highchair waiting for her dinner and looking particularly for her grandmother, whom she calls “Ammanna.”

What happened next profoundly touched me. Mia turned towards her father and said, “

 has an Ouchy!” Clouds of worry eclipsed the joy on her face. She started to suck on her fingers, which is what she does when she is anxious, and stopped being playful. She extended her little hand as though she wanted to touch my face through the phone to reassure herself that I was okay. The band-aid that I had on my face—remnants of a shaving accident on my chin that morning—caused her alarm. I told her I was okay.

Mia had finished with me and turned her attention back to her Ammanna while removing her fingers from her mouth. She began her chant of “

, and chimes” (flower and windchime). My wife apologized to Mia for the delay, and armed with her phone, set out for a walk around our garden to show the colorful flowers. Mooch, our miniature poodle, marched behind.

We have a beautiful flower garden, a moderate-sized deck, and a pergola with a wind chime. By now, Mia had learned to accurately identify each plant’s location in the garden and its flowers’ color. She would exclaim 

 (yellow), red, purple, pink, white, and orange—naming flowers of various varieties as her grandma went around the garden. If her Ammanna missed any color, Mia would demand to see that flower again. While the tour of our garden is in progress, Mia is making sure that her Appa in their kitchen by her side did not miss any of the action by quizzing him, “Did you see that?” Her father answers, “Yes, I did. Did you see that? Isn’t that beautiful?” Mia nods her head to express her appreciation of her father’s attentiveness by saying, “What a guy!”

Mia, her Ammanna, and Mooch finished seeing the flowers to Mia’s satisfaction; her grandmother walked up to the pergola where the wind chime hung. The rods’ continuous chiming made her ecstatic.

As Mia began to eat, somewhat reluctantly, she yawned, looking sleepy and tired. My son said, “Say good night to Tata and Ammanna.” She looked at my son as though she was imploring him to let her stay with us for a few more minutes while fighting a second yawn. My son was firm in his instruction, and Mia said reluctantly good night to us. Also, my ouchy was cured due to the caring and love I saw in her eyes. My wife and I felt sad and turned off the phone with the knowledge that in another 24 hours, Mia would be back again, bringing more joy to her Ammanna and Tata.

Given the past few months’ experience, one could say life is full of tragedies, famines, fires, pandemics, and illnesses. However, it also has beautiful moments. As per Donald Winnicott, MD, the British psychoanalyst, who used the term 

 to refer to the supportive environment that a therapist creates for a client, one can liken holding to the nurturing and caring behavior a mother engages in with her child, which results in the sense of trust and safety in the child.

Due to the advanced modern technology like Facetime, changing lifestyles, and the stresses of contemporary life, the caretaker’s circle can include extended family and friends. Such loving individuals’ involvement will enhance the baby’s self-esteem, diminish her stranger anxiety, and improve her communicational and empathic skills.

In India, where we come from, the elderly and retirees’ lives can be quite hectic because of their active involvement in raising their grandchildren. There’s a cultural acknowledgment that the elderly are repositories of wisdom and life experiences, and 

80% of the elderly live with their children

 For Indians, empty nesting is not a familiar life experience. Grandparents spend their time on family, social, and spiritual activities. The grandchildren learn about living in a complex society through multiple interactions with their elders more than they would in school.

My wife and I came to the United States 42 years ago. As we look into the future, we miss the wise presence of the family elders. We miss the absence of the noise and chaos of India. The silence in empty-nester homes like ours is deafening. The opportunity to witness the development of Mia’s personality is a gift to us from our children. One more day has passed in this endless march of events in the pandemic, but we were able to live our lives without the madness on the streets touching us. Thank you, Mia!

is professor of psychiatry and the Former Von Tauber Chair, Psychiatry & Behavioral Sciences at Nassau University Medical Center.

The Child, the Family, and the Outside World.

2. Biswas S. Why Indians continue to live in joint families. September 14, 2020. Accessed June 22, 2021. 

https://www.bbc.com/news/world-asia-india-54053091

During the pandemic, this psychiatrist is only able to connect to his beloved grandchild through FaceTime. He considers it a blessing. 

The Empty Nesters, The Pandemic, and Mia

 investigated the genetic basis for both migraine and posttraumatic stress disorder (PTSD) by examining identical twins.

Researchers discovered there are common genes and pathways shared by PTSD and migraine, which may suggest they share some risk factors, thus in part explaining the comorbidity of the 2 conditions.

“Our results suggest that common genes and signaling pathways are involved in PTSD and migraine and this might explain why PTSD and migraine can cooccur frequently,” said senior author on the study, Divya Mehta, PhD, of the Queensland University of Technology. “This might further imply that common environmental risk factors for both PTSD and migraine might be acting on these genes.”

The study observed 6 pairs of monozygotic (MZ) twins discordant for PTSD and 15 pairs of MZ twins discordant for migraine. PTSD was measured through phone interviews conducted by an experienced interviewer using structured questions and DSM-IV criteria. All 6 pairs of twins were identified as having experienced a PTSD-qualifying potentially traumatic event as per the DSM-IV criteria. Migraine was assessed using the International Headache Society (IHS) diagnostic criteria, the International Classification of Headache Disorders, ICHD-3, together with a diagnosis of migraine with or without aura. Pairs of twins discordant for migraine with aura were chosen for the study.

Blood samples were taken from all participants. Association between DNA methylation and PTSD status was tested using linear mixed effects models with age, sex, and cell counts as covariates. Using the same study design as the PTSD sample of twins, the 15 pairs of MZ twins discordant for migraine were tested for association of methylation at genetic loci that overlap between PTSD and migraine using varied analyses.

At the epigenome-wide level, researchers assessed how many of the 1036 genes associated with PTSD overlapped with those significantly associated with migraine in the discordant migraine MZ twins.

“We identified DAPK2 and TM6SF2 as two of the top overlapping genes between the two disorders. DAPK2 is a calmodulin-regulated protein kinase, it has been implicated in the intracellular degradation process essential for adaptation to metabolic stress (autophagy). TM6SF2 is associated with cardiovascular disease and plays a role in oxidative stress. These findings suggest that epigenetic changes in response to different types of stress may ‘mediate’ stress phenotypes,” said the study’s authors.

The findings could form the basis for new treatments. Epigenetic changes offer an excellent drug target, as they can often be reversed.

“These results may have implications for treatments, as one medicine or therapy might only be effective for a single disorder,” said Mehta. “For co-occurring disorders such as PTSD and migraine, once we know which common genes are implicated in both disorders, we can develop new therapeutics to target these, thereby reducing symptoms and curing both.”

1. Bainomugisa CK, Sutherland H, Parker R, et al. Using monozygotic twins to dissect common genes in posttraumatic stress disorder and migraine. 

https://doi.org/10.3389/fnins.2021.678350

2. Frontiers. Twin study is first to reveal common genetic risk factors for PTSD and migraine. News release. June 22, 2021. 

https://blog.frontiersin.org/2021/06/22/neuroscience-twins-genes-risk-ptsd-migraine/

Genes may hold the answer to the puzzling comorbidity of migraines and posttraumatic stress disorder. 

Are Migraines and PTSD Linked? 

Jaya Jaya Myra is a best-selling author, TEDx & motivational speaker, and mind-body wellness expert teaching the definitive connections between purpose and health. Her debut book, 

Vibrational Healing: Attain Balance & Wholeness. Understand Your Energetic Type

 is published in 10 languages and available worldwide. Her 2nd book, 

, is slated for publication January 5th, 2021.

Jaya Jaya Myra discusses yoga at large and the philosophy behind it. 

 is a best-selling author, TEDx & motivational speaker, and mind-body wellness expert teaching the definitive connections between purpose and health. Her debut book, 

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International Yoga Day: Mind, Body, Soul Wellbeing 

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 

 Electroconvulsive Therapy in America: The Anatomy of a Medical Controversy 

 The Empire of Depression: A New History 

(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, 

Electroconvulsive Therapy in America: The Anatomy of a Medical Controversy

, 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.

: I suppose some folks, on hearing the title of your new book, may reflexively think, “What…another book about depression? Don’t we have enough of those already?” In your opinion, why was a new history of depression needed?

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

The Noonday Demon: An Atlas of Depression 

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

A couple of long, detailed histories of depression barely mention ECT. This is weird. I know 

—my book about ECT is also about that controversy. However, whatever you think about ECT, many psychiatrists consider it among the best treatments psychiatry has for serious affective disorder. Imagine for a moment a medical historian in another specialty writing a long history of a particular ailment, and then only briefly noting 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.

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 documentation is not really publicly available. I would have liked to do more, but I hope I pushed the field a little in that direction. 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 drew 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, 

 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, although I do give the United States a lot of attention. Anthropologists and global mental health workers have looked at the wider world, but historians really have not done so 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’s 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, say, 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, DSM-5 does not require depressed mood as a necessary criterion for major depressive disorder (MDD), provided there is loss of interest and 4 other symptoms. I draw (lightly) on the concept of family resemblances Ludwig Wittgenstein, PhD: Things do not need precise overlaps to have similarities that justify 

 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.

Overemphasizing cultural differences has its own risks. I show in chapter 1 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 overinsistence 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 Thuminger, PhD, is a great historian of madness with whom I am collaborating on a new project.

She has set forth 4 principles for comparisons 

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.

4. Every individual has an irreducible quality, uniqueness.

I think these are great principles to keep in mind.

: 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 overdiagnosis 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 people look at the high numbers of individuals with a depression diagnosis compared with previous times and take it as self-evident that we are overdiagnosing. It is not. Rising diagnosis rates is a valid reason for concern about overdiagnosis, but it is not proof. In 1950, much of psychiatry was concerned that we were underdiagnosing 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, although 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.

In the book, I offer some defense of antidepressants against their most severe critics. But I also think we are probably overreliant on antidepressants. 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 overreliant 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. However, the idea that depression is purely psychological is, I think, implausible. Yet, so is the view that depression is purely biological. The dichotomy itself is the problem. Mark Solms, PhD, said 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 toward 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.”

 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, however, 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 counterhistory. However, I am not sure the trajectory has been solely drug-driven. When the monoamine oxidase inhibitors and tricyclics were developed, psychiatrists were looking for depression treatments, and they had been doing so for decades. That is partly why these drugs came to be called antidepressants.

One curious thing 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, which started sometime in the 1970s and became more visible in the 1980s. In what I consider the most speculative portion of my book, I try to understand those periods 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.

: You don’t spend much time discussing the creation of MDD as a diagnosis in DSM-III. I wonder how different the 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. In DSM-II, we had diagnoses 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. However, 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.

: 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). This has led to more aggressive pharmacotherapy, such as augmenting with atypical antipsychotics, and the relatively 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, although I think in some cases, the risks may be worth it).

As a historian, however, I would ask if the whole category of TRD does not actually 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.

: In a very memorable passage of your most recent book, you compare history with psychoanalysis: “[P]atients 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.”

 Later, in the epilogue, you again refer to history as a means of guarding against compulsive repetition. Can you summarize what history tells us we can do differently going forward when it comes to 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 continue to do just that, 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 it. 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, although 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 Empire of Depression might help to foster that toleration.

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.

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 

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 a PhD in history from Johns Hopkins University and also studied psychiatric epidemiology at Columbia University. He has authored numerous articles and books, most recently 

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

The Noonday Demon: An Atlas of Depression

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

Is depression the same today as it was in the 17th century? Is it the same thing in Nigeria as it is in the United States? One of the foremost historians of psychiatry weighs in. 

Exploring the Evolution of Depression

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is a family physician, a certified therapist, and medical and therapeutic services director at 

Posttraumatic stress disorder (PTSD) can be exceptionally 

. But recent studies have suggested the efficacy of a surprising option: 

For PTSD, 3,4-methyl​enedioxy​methamphetamine (MDMA) appears to be especially 

. In this Mental Health Minute, Devon Christie, MD, CCFP, IFMCP, RTC discusses her latest study results on this topic and what might be in the future for psychedelic-assisted psychotherapy.

Do you have patients who might benefit from MDMA-assisted psychotherapy? 

Share comments with your colleagues by emailing 

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

A growing body of scientific evidence suggests that mind-altering drugs, combined with psychotherapy, are effective treatments for some of the most stubborn psychiatric disorders.

What Does the Future Hold for Psychedelic-Assisted Psychotherapy?

is an author, motivational speaker, artist, board-certified OB/GYN and reproductive endocrinologist, and Founder and Director of CNY Fertility, one of the largest and most dynamic fertility centers in the country, featured in the Wall Street Journal, Today Show, and CNBC for helping shape the future of fertility medicine. With more than three decades of experience, Dr. Kiltz has developed cutting-edge protocols grounded in Western medicine and supported by Eastern practices, and changes to diet and lifestyle. While working with patients on dietary and lifestyle changes for fertility, Dr. Kiltz discovered that he was simultaneously helping hundreds with other medical problems (diabetes, IBS, chronic migraines, and much more). He has earned recognition outside of the fertility world for pioneering the holistic health movement and the keto lifestyle. In addition to his own media outlets, Dr. Kiltz appears regularly on numerous popular blogs and has shared his views as a TEDx speaker.

Robert Kiltz, MD, gives some ideas of how physicians can tend to their own wellness. 

is an author, motivational speaker, artist, board-certified OB/GYN and reproductive endocrinologist, and Founder and Director of CNY Fertility, one of the largest and most dynamic fertility centers in the country, featured in the Wall Street Journal, Today Show, and CNBC.

You must take care of yourself before you can take care of others. 

Improving Life as a Physician

Modern psychiatry—and modern psychopharmacology—is a relatively young field. In fact, the word antidepressant was coined in 1952, tranquilizer in 1953, and antipsychotic was first used at a medical meeting in 1956—and the acceptance of all was slow. Over the next 2 decades, these types of medicines were developed. Interestingly, most of the drug discoveries occurred inadvertently, often beginning with a chance observation by a physician or scientist who was looking for something else.

Many key figures in modern psychopharmacology were caught up in World War II in some way.

, of France, who initiated the use of chlorpromazine for psychoses, and Australian John Cade, MD, who made the modern rediscovery of lithium for bipolar disorder, were military physicians. In both cases, wartime experiences obviously influenced their work. Laborit was aboard a French destroyer struck by torpedoes during the evacuation of Dunkirk and was awarded a Military Cross for his actions during its sinking. After the development of chlorpromazine, he quickly suggested that it might be useful in managing stress in wounded soldiers on the battlefield (which proved to be an unsuccessful, even disastrous, endeavor). Meanwhile, Cade volunteered to serve in the Australian Army; he was stationed in Singapore until he was captured and spent several years as a prisoner of the Japanese. While caring for fellow prisoners of war, he noticed fluctuating levels of mental clarity and wondered if this phenomenon was related to changing amounts of substances circulating in thsubstances, foreshadowing the later studies he performed that led to lithium’s use in what was then called manic depression.

, who went on to discover meprobamate, the first modern tranquilizer, was a young physician in the Czechoslovakian National Institute of Health who fled Nazi occupation of his country. Arriving in Britain in 1939, he first worked providing medical care in refugee camps. Leo Sternbach, PhD, born in what is now Croatia, was an organic chemist who had experienced anti-Semitism firsthand in Poland. He was working for Hoffmann-LaRoche Company in Basel, Switzerland, when Germany invaded Greece and Yugoslavia in 1941. Facing an increasingly precarious situation, he fled through France and Portugal and came to the United States, where he discovered the first benzodiazepine tranquilizer. Chemist 

, who worked on Britain’s secret atomic bomb research and served in the Home Guard when away from the laboratory, later applied some of his newfound techniques to develop the anesthetic halothane.

Other influential scientists emerged from earlier battles. William A. Hammond, MD, who made observations with lithium in bipolar disorder in the 1870s, was Surgeon General of the Union Army during the American Civil War.

 Hans Berger, MD, served in the German cavalry in 1892 and was almost killed in a riding accident. His resulting curiosity about the workings of the nervous system led to the discovery of human electroencephalography. His story continued and ultimately included suffering at the hands of the Nazis, who took over his university in the 1930s. Constantin von Economo, MD, the Austrian psychiatrist and neurologist who described encephalitis lethargica and the role of hypothalamic structures in sleep and waking, was an army pilot in northern Italy in 1916.

 Charles Sherrington, FRCP, FRCS,whose studies with Edgar Adrian, MD, clarified the processes of nerve cell communication, worked in a shell factory 13 hours a day during World War I, while Adrian treated war casualties at St Bartholomew’s Hospital in London. Alexander Fleming, FRS, FRCS, whose later discovery of penicillin profoundly affected psychiatry by providing a treatment for tertiary syphilis, served in World War I, in which his studies of evolving wounds led to his later discoveries.

The broader field of neuroscience developed in the post–World War II years, with its founders having pivotal wartime experiences. Otto Loewi, PhD, whose experiments confirmed chemical transmission across synapses, was imprisoned by the Gestapo on the night of the German invasion of Austria. He was stripped of all his possessions, but he was later allowed to emigrate on the condition that he transfer the funds from the Nobel Prize he had earned in 1936 to a Nazi-controlled bank.

 An American self-taught scientist, Alfred Lee Loomis, DSc, JD, discovered the K-complex in the electroencephalograph and first classified the sleep stages, then went on to play a crucial role in developing military radar in World War II.

 Sir Alan Lloyd Hodgkin’s experiences living in wartime Britain, and involvement in radar research impacted him so deeply that much later, at age 78, he felt the need to return to the World War II years in his last major work, 

Chance & Design: Reminiscences of Science in Peace and War

 As a medical student, Arvid Carlsson, MD, PhD, examined concentration camp prisoners who had been released to neutral Sweden. The encounter so impressed him that he talked about it at length in the biography he wrote to accompany his Nobel Prize 56 years later. Starting in his 60s, Laborit wrote extensively on the applications of neuroscience to aggression and violence.

The remarkable thing about these stories is the variability of these experiences.

 Sometimes the war represented more of a hiatus in ongoing research, which was later resumed. In other cases, it led to displacement or imprisonment. Sometimes the result was devastating and culminated in suicide, while in other cases it was a stimulus leading to advances in research. It is a good reminder that, sadly, war is intimately involved in the human condition, and more specifically, that in order to understand the blossoming of neuroscience and psychopharmacology in the 1950s and 1960s, it is useful to take into account the wartime experiences of the founders.

is a professor of psychiatry and clinical pharmacology (ret) at the University of Chicago. His recent books include

Molecules, Madness, and Malaria: How Victorian Fabric Dyes Evolved into Modern Medicines for Mental Illness and Infectious Disease

Nepenthe’s Children: The History of the Discoveries of Medicines for Sleep and Anesthesia

Portions of this article are adapted from

The Curious History of Medicines in Psychiatry

Trial by Fire: World War II and the Founders of Modern Neuroscience and Psychopharmacology

Molecules, Madness and Malaria: How Victorian Fabric Dyes Evolved into Modern Medicines for Mental Illness and Infectious Disease

4. Hodgkin A. Chance & Design: Reminiscences of Science in Peace and War. Cambridge University Press; 1992. ❒

Sometimes the war represented more of a hiatus in ongoing research, which was later resumed. In other cases, it led to displacement or imprisonment.

War—What Is It Good For? Perhaps Modern Psychopharmacology

For several years my colleagues and I have pursued a simple question with profound implications for psychiatric practice: how does psychotherapy work? We want to capitalize on major advances in our understanding of the neural basis of memory, emotion, and emotion-memory interactions. If we could start to explain the basic mechanism of action behind psychotherapy, then maybe we could understand how to conduct psychotherapy more effectively, with the ultimate goal of working with our patients to produce lasting changes in their mental health.

Recent studies have made important discoveries about the neural mechanisms underlying memory. Four are of particular interest. First, memories are not fixed entities; rather, they enter a labile state whenever they are reactivated, and can be modified or updated with new information during a 4 to 6 hour window after 

 Second, specific episodic (event) memories and semantic (generalizable knowledge) memories are highly inter-related in that they share neural mechanisms, and the latter are a distillation of the 

 Third, memories that are emotionally charged are remembered better than 

 And fourth, the activation of emotion appears to be a necessary ingredient of successful outcomes in 

Drawing upon these observations, my colleagues and I hypothesized that there were 3 key ingredients to lasting change in psychotherapy: 1) activating problematic memories and the associated painful affect; 2) concurrently engaging new emotional experiences that change old memories through reconsolidation; 3) reinforcing the strength of new memories and their semantic structures by practicing new ways of behaving and experiencing the world in a variety of contexts. In a 2015 article in a leading neuroscience 

 we briefly discussed the application of this model to 4 different psychotherapy modalities, including behavioral, cognitive behavioral (CBT), emotion focused (EFT), and psychodynamic psychotherapies..

Diving Into the Research—and the Clinical Implications

Realizing that there was much more to say about this new way of understanding change in psychotherapy, my colleagues and I published an edited volume, with multiple contributors, that both explains the basic science of memory and outlines a clinical application of our model. The new book, 

Neuroscience of Enduring Change: Implications for Psychotherapy

, expands upon the previous work in 3 sections.

 The basic science section includes chapters on emotion, memory, emotion-memory interactions, the role of language in shaping emotion and memory, and the role of sleep in memory consolidation and reconsolidation. The clinical section includes chapters from leading experts in psychodynamic psychotherapy, CBT, EFT, coherence therapy, and integrative approaches. Each author considers the role of memory reconsolidation in both psychotherapy and in achieving lasting personal change. The final section includes chapters on recurrent maladaptive patterns, a computational neuroscience perspective on the proposed model, and a discussion of a proposed preclinical and clinical research agenda.

Considerable effort was made within and across chapters to promote cross-fertilization between basic science and clinical application. Although it is written for neuroscience-oriented mental health clinicians, all psychotherapists, psychotherapy researchers, and scientists interested in memory, emotion, and their clinical application will find new ideas and practical advice in this book. An independent 

If one takes this model seriously it could influence psychiatric practice in several ways. For example, it is useful to consider how interventions might be adjusted in therapies that have stalled or have failed. Rather than talking about feelings with the goal of promoting insight, it is also important to experience feelings, especially the old painful feelings from which individuals have protected themselves for years, and to juxtapose these feelings with corrective emotional experiences.

Another clinical implication emerges from the observation that consolidation of emotional memories occurs primarily during REM sleep. Because reconsolidation may work in the same way, medications that inhibit REM sleep may be counterproductive to enduring change in psychotherapy. It is therefore important to know that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitor, tricyclics, and benzodiazepines inhibit REM sleep, whereas trazodone, buproprion, and 

. The book describes these and other implications and provides a fresh perspective on how psychotherapy practice may be optimized and integrated in psychiatric care.

My interest in this topic emerged over the course of my 35-year career as an academic psychiatrist. I was initially trained as a clinical psychiatrist and psychodynamic psychotherapist and have continued to practice and supervise residents ever since. I was also fortunate enough to receive research training (resulting in a PhD in experimental psychology) that focused on cognitive neuroscience and functional neuroimaging of emotion. I have found the dialogue between the basic science of psychiatry and its clinical application to be particularly enriching and informative.

In my role as educator, I have become well acquainted with the challenges (eg, significant differences in the theoretical backgrounds, mindset, and clinical interventions required by these different approaches) psychiatry residents face in developing competence in CBT, psychodynamic psychotherapy, and supportive psychotherapy. Because there is a strong interest in finding common factors and common mechanisms across psychotherapy modalities, it occurred to me that a systems neuroscience perspective could provide an integrative mechanistic framework that would highlight commonalities instead of divergences. Moreover, the goal of integrating pharmacotherapy and psychotherapy is likely to be advanced by explaining how each works in brain-based terms. In my efforts to develop a new brain-based model of change in psychotherapy, I have been fortunate to have remarkable collaborators, including Lynn Nadel, PhD, Emeritus Professor of Psychology at the University of Arizona (a pioneer in the newly emerging understanding of memory).

It is important to emphasize that we have not yet established that change in psychotherapy occurs through memory reconsolidation. One of the conclusions of our book is that a focus of intervention is recurrent maladaptive patterns, which can be understood as an expression of schemas. Schematic memory is a type of semantic memory and, as an area of neuroscientific investigation, it is relatively new. It remains to be demonstrated empirically that schematic memories can be updated with emotional information. If so, it must then be determined whether this applies to psychotherapy. Although research of this type is still underway, it might be argued that it is important to consider the clinical implications of this model if it were true.

is professor of psychiatry, psychology, and neuroscience at the University of Arizona.

1. Phelps EA, Hofmann SG. Memory editing from science fiction to clinical practice. 

2. Ryan L, Hoscheidt S, Nadel L. Perspectives on episodic and semantic memory retrieval. In: Dere A, Easton J, Huston J, Nadel L, eds. 

3. Kalbe F, Schwabe L. Beyond arousal: Prediction error related to aversive events promotes episodic memory formation. 

4. Lane RD, Ryan L, Nadel L, Greenberg L. Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science. 

5. Auszra L, Greenberg LS, Herrmann I. Client emotional productivity-optimal client in-session emotional processing in experiential therapy. 

7. Kramer U. Review of “Neuroscience of Enduring Change: Implications for Psychotherapy.” 

8. Doghramji K, Jangro WC. Adverse effects of psychotropic medications on sleep. 

9. Borbély AA, Mattmann P, Loepfe M, Strauch I, Lehmann D. Effect of benzodiazepine hypnotics on all-night sleep EEG spectra. 

A brain-based perspective could explain how and why psychotherapy leads to enduring change. 

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