Barbara Schildkrout, MD

by Karl Deisseroth, MD, PhD; Random House, 2021

On September 27, 2021, the prestigious Lasker Award was presented to a psychiatrist: Karl Deisseroth, MD, PhD, of Stanford University. Deisseroth’s recently published book, 

 is not only a joy to read; it is also a compelling, educational experience. I recommend it to every 21st-century psychiatrist. Here’s why.

Deisseroth’s book is a beautifully written memoir about this gifted psychiatrist’s work with patients, focusing on those who pierced his professional armor and shook him to the core. But we have all read books like this—books that are wonderfully evocative of the profound experiences we have had with patients. This book is like that. It is also more.

Ever since George Engel introduced the biopsychosocial model in 1977,

 physicians have been challenged with the difficult task of conceptualizing a patient’s psychological dynamics, life situation, and biology as entirely intertwined and virtually inseparable. Deisseroth achieves that integration in his thinking. His sophisticated formulations incorporate multiple dimensions and the influence of each on the others. His narrative moves effortlessly from thoughtful, personally revealing descriptions of patients to insights about behavior that are infused with an understanding of cultural context, brain functioning, and the long process of genetic evolution.

From a young age, Deisseroth was absorbed with narrative—the creative use of words through poetry, literature, and writing. Later, in college and medical school, he also found himself interested in scientific approaches that looked at how single units assembled into complex systems—neural networks, for example (though language also comes to mind). Deisseroth had 

Addressing Challenging Moments in Psychotherapy: Clinical Wisdom for Working with Individuals, Groups and Couples

An Integrative Paradigm for Mental Health Care: Ideas and Methods Shaping the Future

Science Over Stigma: Education and Advocacy for Mental Health

But, on Deisseroth’s first day of his psychiatric rotation, a patient burst into the nurses’ station and focused an emotional out-pouring on Deisseroth. “In arm’s reach, standing above me, he fixed his gaze to mine—his eyes wide in fear and rage… [T]he hurt was bright in his eyes; the terror was real.”

 What most struck Deisseroth, the medical student, was the patient’s speech. “…[I]t was creative in its agony, full of phrases used not for traditional meaning, but seemingly for their own sake, as communicative effects, with their own grammar and aesthetic, self-contained. …He spoke a novel word that sounded like one in a phrase of Joyce’s I had read long ago. …He evoked in me science and art together, not in parallel, but as the same idea, fused…”

Deisseroth had always been interested in words, and here, in this encounter, it became clear to him that psychiatric illness was manifested through a patient’s emotional communication. Everything came together for Deisseroth and reset the course of his career. He writes, “…[W]hat, in fact, are those feelings, in a physical sense, down to the level of cells and their connections? This struck me as perhaps the most profound mystery in the universe—rivaled only by the question of the universe’s origin, its reason for being.”

Deisseroth’s encounters with patients become opportunities for self-reflection, curiosity, and keen observation; they also provide the grounding for discussions about the neural underpinnings of behavior. Deisseroth’s descriptions of neuronal functioning are lucid and vivid; they have narrative life. Far from the dry, rote, lessons about neuroscience to which we have become accustomed, Deisseroth’s deep understanding makes his explanations of brain function entirely lively and memorable.

Throughout, Deisseroth appreciates and captures the full breadth of psychiatry—from the astonishment he felt upon hearing a thought disorder (a first glimpse at the multitude of extraordinary ways that mental functioning can go awry), to the counterintuitive behaviors of someone afflicted with an eating disorder, to the power of human connection and the magic of creativity. Deisseroth reminds us of the profound mysteries of human behavior that called many of us to pursue careers in psychiatry.

But Deisseroth did not win the Lasker Award for any of this. The award was given to him for his work with colleagues in pioneering a revolutionary approach to studying individual neurons in living mammals—a technique known as optogenetics. Deisseroth’s book makes the fundamental concepts of optogenetics easy to understand.

Algae contain proteins that transform light into energy; this is how these organisms produce energy for survival. Optogenetics takes the genes that code for these proteins and transfers them into mouse neuronal DNA. This makes it possible for a researcher to turn individual mouse neurons “on” or “off” by exposing them to light delivered through fiber optics that have been inserted into the mouse brain. Switch “on” the light—switch “on” a neuron. This can be used, for example, while simultaneously observing the animal’s behavior and thereby discerning the specific neuron’s function.

This methodology has proven to be extraordinarily powerful as an investigative tool. In 2009, there were 25 papers listed in PubMed under the search term, “optogenetics;” by 2016, there were over 900, and so far in 2021, there have been well over 1,000.

In his book, Deisseroth shows us how his work with patients and his curiosity led to important scientific questions. These questions, in turn, fueled his prolific neuroscience research and have influenced scientific work around the world.

, the book’s title, refers to a defense mechanism, well-known to psychiatrists, in which aspects of the self are experienced by the individual as residing outside the self. But 

 also are the ultimate destination of a neuron—the anatomical site to which a neuron extends its axon and exercises its synaptic influence.

 is a work of true biopsychosocial integration. Karl Deisseroth is a model and an inspiration for all of us in the field of psychiatry.

is an assistant professor of psychiatry, part-time at Harvard Medical School in the Department of Psychiatry at Brigham and Women’s Hospital. She is the author of several books and a blog.

The need for a new medical model: a challenge for biomedicine.

. Random House Publishing Group; 2021:8-10.

Articles

Karl Deisseroth's new book is a compelling, educational experience.





Projections: A Story of Human Emotions

Loss of the sense of smell—anosmia—can be devastating. Without smell, patients describe feelings of emptiness, isolation, and emotional distress. Given that anosmia is a common first symptom of COVID-19 and a long-term sequela for as many as 10% of patients who have had COVID-19– related anosmia, psychiatrists need to be familiar with this symptom in order to identify and manage the associated psychological effects.

Prior to the current pandemic, anosmia and hyposmia (decreased sense of smell) received little attention in the popular press or in the non–ear, nose, and throat (ENT) medical literature.However, disturbances in the sense of smell have become a widespread focus of concern now that anosmia has emerged as a possible first symptom—and sometimes the only symptom—of infection with the SARS-CoV-2 virus. 

For most individuals who have a COVID-19–related loss of smell, the deficits are short-lived. But for those individuals who do not fully recover, the neuropsychiatric consequences can bedebilitating. Pleasures of eating are lost when one cannot detect the complex scents of food. Atmospheric odors disappear: the smells of the kitchen and garden, the gym, the sea. 

 may ensue without the ability to detect signals of danger (eg, smoke, gas, spoiled food). It is not uncommon for 

The pandemic-related increase in the prevalence of anosmia has thrown its debilitating effects on mood and quality of life into sharp relief and presents an opportunity for psychiatrists to help. 

The SARS-CoV-2 virus was first reported in December 2019, although the association between anosmia and this viral infection initially was not made. Then, in late March 2020, 

Hopkins and Kumar sent a bulletin to Public Health England

, noting high rates of COVID-19 infection “amongst ENT surgeons compared [with] other health care workers.”

 They reported that physicians and surgeons from around the world had noticed a significant increase in the number of otherwise asymptomatic individuals who were presenting with an abrupt onset of anosmia. They hypothesized that these patients could be unsuspected carriers of the SARS-CoV-2 virus and advised the use of full personal protective equipment for clinicians examining any patient withanosmia.

During this early stage of the pandemic, individuals across the globe did not qualify for COVID-19 testing if their only symptom was anosmia; however, in countries where testing waswidespread, patients who tested positive for COVID-19 often had anosmia, and frequently anosmia was their first symptom. By April 2020, the Centers for Disease Control and Prevention had added sudden loss of smell and/or taste to the diagnostic criteria for COVID-19. Both subjective and objective evidence for 

 have now been documented in up to 80% of patients with COVID-19.

It is now known that abrupt loss of smell may be an early, and possibly the only, symptom of SARS-CoV-2 virus infection. While anecdotal reports of anosmia abound, scientific studies of outcome are limited. Published research to date indicates that approximately 25% of individuals continue to have disturbances in their sense of smell for 

; fewer than 15% of individuals have disturbances in their sense of smell by 2 months; and up to 10% of individuals have a protracted course of recovery or 

may not fully recover their sense of smell

 Given that confirmed SARS-CoV-2 infections have reached more than 33 million cases in the United States and more than 

 more than 3 million individuals could be left with some deficit in this sensory modality in the United States.

pathophysiological theories to explain COVID-19 anosmia

. The most plausible explanation is viral infiltration of support cells of the olfactory epithelium (sustentacular cells), inflammation, and 

 The sustentacular cells of the olfactory epithelium are especially vulnerable to viral damage due to having a high density of ACE2 cell surface receptors. The ACE2 receptor is a known entry point for the COVID-19 virus. 

, the pathway to regaining olfaction may be marked by experiences of unpleasant, distorted, and often repugnant smells (parosmia). In somecases, individuals may have hallucinatory smells (phantosmias). The mechanisms that underlie these phenomena are still unclear but may be related to imbalanced rewiring of regenerating olfactory neurons or immaturity of neuronal networks when stem cells have been recruited to replace damaged olfactory neurons.

The sense of smell is neurologically a function of cranial nerve I and distinct from the neurological basis of taste, which is a function of cranial nerves VII, IX, and X. The subjective experience of taste, however, is extremely complex and may be altered with changes in sense of smell. Taste involves the basic sensations of sweet, sour, salty, bitter, and umami in addition to the somatosensory experiences of temperature, touch, pressure, and pain (spiciness) (

). The experience of taste also includes sensations from odorants that are presented through the nostrilsand/or via the nasopharynx. 

 Factors Contributing to the Experience of Flavor

Before the current pandemic, about 3% of the adult population aged 40 years or older and up to 22% of adults aged more than 60 years were 

 Patients with neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and dementia with Lewy bodies exhibit a gradual loss of the sense of smell; often these individuals are only minimally aware of their deficit. The abrupt loss of a sense of smell can occur with head trauma or with any of numerous viral infections, including infection with SARS-CoV-2 (

When there is a sudden loss of the ability to smell, patients are startled by how important scents are to their daily life experience. This sudden alteration in one’s experience of the environment is unsettling and often deeply emotionally distressing. Even before this pandemic, researchers had documented the negative effects that anosmia has on mood, 

Possible Psychological Consequences of Anosmia

Since the pandemic, newspapers and magazines have published essays by individuals who have 

personally experienced COVID-19 anosmia and parosmia

. The authors widely report a loss of pleasure in eating. For example: “It was first apparent that something was wrong when I took a bite of a falafel sandwich that morning and it hung like tasteless cardboard in my mouth.”

 These writers also comment on changes in weight and disruption to patterns of social engagement that center around sharing a meal. 

Some of the articles focused on individuals who depended on the sense of smell for work: chefs, firefighters, and perfumers. 

Sommeliers commented on their experiences

: “It was absolute terror. The thought of no longer being able to do so much of my job was just terrifying. And then there’s everything else in your life. I love to cook, I love more than just wine, and all of that would be gone.”

The loss of smell sensations also affected individuals in ways that are difficult to define: “I feel alien from myself... It’s also kind of a loneliness in the world. Like a part of me is missing, as I can no longer smell and experience the emotions of everyday basic living”

—like I don’t exist. I can’t smell my house and feel at home. I can’t smell fresh air or grass when I go out. I can’t smell the rain.”

. He quotes a patient as saying, “This strange, empty feeling makes me feel weird about my body.”

 The other patient was aware of feeling “distant from the world, without atmospheric cues deriving from environmental triggers.”

Although smell is arguably the least appreciated of our senses, it is extraordinarily fundamental. The sense of smell is neurologically (and, therefore, experientially) involved in memoryformation, emotional processing, and social behavior. 

Smelling is inextricably entwined with breathing

, just as tasting is inextricably entwined with swallowing.

 Smell is a source of extraordinarily complex, often nonconscious, information about our environment, including our social environment. We smell our babies; we smell our partners; we know the smell of our ownbodies. Intimate relationships may be disrupted by disturbances in the sense of smell. 

. Although it followed a traumatic brain injury (TBI), the description could apply to post–COVID-19 anosmia

Sense of smell?...I never gave it a thought. … But when I lost it—it was like being struck blind. Life lost a lot of its savour—one doesn’t realize how much “savour” is smell. You smell people, you smell books, you smell the city, you smell spring—maybe not consciously, but as a rich unconscious background to everything else. My whole world was suddenly radically poorer.

Over time, as neurological functioning returns to normal, some individuals may experience distorted sensations of odorants (parosmia) or hallucinatory smells (phantosmias). Often these sensations are repellent and 

However, the most unbearable is tap water. Showering, rinsing dishes, brushing my teeth, washing my face, and many more daily encounters are now repulsive and unbearable. Living in a world where tap water smells putrid has been one of the hardest things I’ve ever gone through.

My sweat acquired an acrid rotting-veggie–like fetid smell—swamp-like, but acidic and sharp.

Of paramount importance is the psychiatrist’s role in listening to patients, gaining an understanding of anosmia’s effects on their quality of life. While anosmia may be an acute or chroniccondition, in either case, managing related health problems and maximizing quality of life are key goals of treatment. 

In addressing the patient’s health problems, psychiatrists should first clarify the anosmia etiology, then identify and treat any comorbid psychiatric conditions, such as anxiety and depression. Anosmia may exacerbate an already existing mental health disorder. It is also important to determine whether a patient has been able to maintain good nutrition, hydration, and stable weight.

Other health-related issues relate to personal hygiene and guarding against breath and body odor—with important social implications. Changes in relationships and intimacy can result from anosmia because of the complex relationship linking scents and social bonding. While a lack of awareness of one’s body odor can lead to poor hygiene and interfere with personal relationships, an inability to detect a partner’s scent can also negatively influence a feeling of attraction. 

Like our senses of vision and hearing, our sense of smell serves not only to bring pleasure from pleasant smells and taste, but also to protect us from danger. Anosmia can make one unaware of the presence of dangerous inhalants like smoke, natural gas, and harsh cleaning ingredients. Spoiled food can go undetected, be consumed, and lead to illness. Thus, part of counseling an individual about the management of anosmia should also include advice about prevention of injury and illness. Recommendations may include installing smoke and natural gas detectors, regular maintenance to gas appliances, and dating food when opened to anticipate spoilage. Also, asking others to smell for noxious odors of any kind can be helpful.

Psychiatrists might wish to refer patients for consultation for help in managing the consequences of anosmia. If an individual’s occupation is at risk due to loss of ability to detect scents, career counseling may be useful. Individual, couples, or family therapy might be helpful, with an emphasis on education regarding anosmia and its effect on close relationships. 

Smell training is the one treatment approach that directly addresses anosmia. Smell training aims to enhance the natural process of recovery by a program of consistently sniffing and concentrating on a small sample of scents multiple times a day over a period of months. The scents may be purchased as a kit, or a set of samples can be homemade.

Referrals to otolaryngologists who specialize in anosmia may be appropriate, especially for those with severe symptoms, or if there is uncertainty about the underlying cause. Many hospital-based otolaryngology departments have clinics that specialize in patient care for disturbances of smell, some of which offer smell training. 

The Global Consortium for Chemosensory Research was founded in response to the outbreak of COVID-19–related anosmia. Its website has become a hub for researchers and is an easy way for patients who are interested to participate in research.

, which was published in 2010 as part of the 

 Although it was written before the currentpandemic, this book is nonetheless useful for individuals with COVID-19–related disturbances in smell and taste. Written for a general audience, it includes numerous recipes that were developed to emphasize aspects of the food experience to enhance the pleasure of eating for those with disturbances in the experience of taste. Nutritionists also may be able to advise patients on how to modify food preparation and seasoning to emphasize aspects of taste that do not rely on smell.

Several websites by nonprofit organizations offer support to those suffering with anosmia. Fifth Sense and AbScent are charities in the United Kingdom aimed at helping those with anosmia. They have advice about smell training, as well as community forums and Facebook groups, ranging from general support groups to those with a more specific focus, such as COVID-19–related anosmia or parosmia/phantosmia. These online resources make it possible for patients to share their experience of loss with others while also obtaining advice on how to cope with symptoms.

, patients rarely discussed loss of smell with their psychiatrists. For patients with postviral anosmia, an ENT specialist was most often consulted, not apsychiatrist. For patients with loss of smell from neurodegenerative diseases, the onset of anosmia is insidious and generally not a major focus of concern for the patient. For patients with TBI, the loss of smell is abrupt, but often pales in comparison with other, more salient disabilities. Because of COVID-19, however, millions of individuals have been affected by anosmia from COVID-19, including patients who seek psychiatric consultation for other concerns.

It is important for practitioners to understand the full spectrum of smell-related disturbances so they can be maximally helpful to patients. In some cases, anosmia or parosmia might be contributing to the psychiatric presentation. Psychiatrists need to be familiar with what is known about the natural course of COVID-19–related anosmia, approaches to ensuring safety and facilitating recovery, and how to help patients to find resources.

Perhaps most importantly, psychiatrists need to appreciate the depth of emotional disturbance that a loss of smell brings and the destabilization that ensues when one’s world suddenly lacks an important dimension; this is especially true for patients who might already have eating disorders or difficulties with feeling safe in the world. Along with practical advice, psychiatrists might facilitate the articulation of this complex experience. We also can offer empathy and validation to patients.

(This article has been updated to correctly attribute the quotes from reference No. 16--Ed.) 

is an assistant professor of psychiatry at Harvard Medical School in the Department of Psychiatry at Brigham and Women’s Hospital; she is the author of several books and a blog.

is an adjunct assistant professor at the University of Maryland School of Medicine and is the director of The Concussion Clinic at Sheppard Pratt.

is an assistant professor at the University of Toronto and a staff psychiatrist at the University Health Network.

is a neuropsychiatrist in Wellesley, Massachusetts; she also serves on the Harvard Medical School faculty and on staff at Brigham and Women’s Hospital.

1. Coelho DH, Reiter ER, Budd SG, et al. 

Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

Olfactory disorders and quality of life—an updated review.

3. Hopkins C, Kumar N. Loss of sense of smell as marker of COVID-19 infection. ENT UK/Royal College of Surgeons of England. 2020. Accessed June 1, 2021. 

https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf

Olfactory dysfunction: a highly prevalent symptom of COVID-19 with public health significance. 

5. Printza A, Katotomichelakis M, Valsamidis K, et al. 

Smell and taste loss recovery time in COVID-19 patients and disease severity. 

6. Parente-Arias P, Barreira-Fernandez P, Quintana-Sanjuas A, Patiño-Castiñeira B. 

Recovery rate and factors associated with smell and taste disruption in patients with coronavirus disease 2019. 

7. Johns Hopkins University & Medicine: Coronavirus Resource Center. Accessed June 1, 2021. 

Smell and taste disorders in COVID-19: from pathogenesis to clinical features and outcomes.

COVID-19 and anosmia: a review based on up-to-date knowledge.

COVID’s toll on smell and taste: what scientists do and don’t know.

11. Boesveldt S, Postma EM, Boak D, et al. 

12. Kollndorfer K, Reichert JL, Brückler B, et al. 

Self‐esteem as an important factor in quality of life and depressive symptoms in anosmia: a pilot study.

Assessing the impact of anosmia: review of a questionnaire’s findings.

. September 12, 2015. Accessed June 1, 2021. 

https://www.theatlantic.com/health/archive/2015/09/world-without-scent-smell-anosmia/404749/

15. Camuto R, Harans J. What’s a sommelier to do when they lose their sense of smell? 

https://www.winespectator.com/articles/what-s-a-sommelier-to-do-when-they-lose-their-sense-of-smell

16. Burges Watson DL; Campbell M, Hopkins C, Smith B, Kelly C,  Deary V. Altered Smell and Taste: anosmia, parosmia and the long impact of Covid-19. Accessed August 30, 2021. 

 (accepted for publication). Preprint available at 

https://www.medrxiv.org/content/10.1101/2020.11.26.20239152v1.full.pdf

Importance of SARs-CoV-2 anosmia: from phenomenology to neurobiology. 

19. Parosmia: “The smells and tastes we still miss, long after Covid.” BBC News. February 6, 2021. Accessed June 1, 2021. 

https://www.bbc.com/news/stories-55936729

Loss of smell can be devastating for patients. How can psychiatrists deal with the associated psychological effects? 

COVID-19 Brings Anosmia to the Attention of Psychiatrists

A complete, accurate, and timely diagnosis is the cornerstone around which effective treatment is constructed. Yet, the complex skills involved in the art and science of diagnosing have only been the focus of investigation for less than a decade.

While the process of diagnosing is common to all fields of medicine, this article specifically addresses missed “medical” diagnoses in patients who present to or are being followed by psychiatrists and other mental health clinicians. It is hoped that by learning about vulnerabilities within the diagnostic process, readers will have the opportunities to reduce diagnostic error rates in their own practices and institutions.

Diagnostic errors and delays are so widespread that most individuals will experience a diagnostic error during their lifetime.

 And surely, every physician has had the experience of missing a diagnosis or coming to the correct diagnosis only after too long a delay. Memories of missed opportunities for earlier intervention weigh heavily upon us.

What Is the Correct Diagnostic Formulation In Neuropsychiatric Practice?

Recent studies have found that any individual with a “psychiatric history” or with “presenting symptoms in the sphere of mental functioning and behavior” is especially prone to experiencing a diagnostic error.

 This should alert all psychiatrists, since these are the very patients we are called upon to see. Rare diseases might be misdiagnosed, but, more often, common diseases are missed, especially if they present atypically.

In 2015, an Institute of Medicine report-

-concluded that, “. . . improving the diagnostic process is not only possible, but presents a moral, professional, and public health imperative.”

How do doctors make a diagnosis? As you read the following vignette of a referral, try to be aware of your diagnostic hypotheses.

According to his primary care physician (PCP) who referred him, Mr O has a long history of psychosomatic complaints. Mr O is a 63-year-old accountant who recently retired. He’s been sleeping restlessly and waking up depressed each morning. He jogs a few miles a day, most days, but says that lately he’s been feeling stiff and somewhat unsteady on his feet. Also, he says he’s “plagued by” constipation. The patient told the PCP that he can’t tell whether these physical problems are “all in my head” or whether there’s really something to worry about.

When you get a referral, you are presented with a great deal of information, and it isn’t clear which information will be relevant to your eventual understanding of the patient’s health problems. Some of the material that is contained in the referral will be explicit, some implied, details may be inaccurate, and surely, much will be left out.

Now consider that once you greet a patient in the waiting room, you will have even more information. You will notice how the patient is dressed and what he’s been doing while waiting; you will observe his facial expression, level of social comfort, his gestures and gait. And, before you even hear the patient’s voice or ask a single question, all of these experiences will affect you and have an influence on how you are inclined to think about the diagnosis.

Diagnostic problem solving is extremely engaging for physicians, but it is not the defined type of problem solving one encounters with something like a crossword or Sudoku puzzle in which there are 26 letters or 9 numbers that are manipulated to form one unique solution. Making a diagnosis is complex problem solving in an uncertain domain. Any particular information or observation might be relevant; and any particular information or observation might be irrelevant (noise). The patient might leave out crucial parts of the illness story, perhaps not realizing that they are important. Or the physician–problem-solver may have insufficient knowledge, perhaps never having heard of the diagnosis that actually explains the patient’s symptoms. There also could be more than one diagnosis; and these diagnoses might be interacting with one another.

The reigning theory about diagnostic problem solving is that it involves two interacting cognitive systems-system 1 and system 2.

System 1 cognition is illustrated by the experience of seeing a patient for the first time and “knowing” immediately that the patient has, for example, schizophrenia. System 1 is based on mental pattern-recognition; it is intuitive, but honed and refined by experience; it is fast, effortless, and operates outside of awareness. While this system is extraordinarily efficient, processing large amounts of information very rapidly, it is also highly error-prone and open to biases (predispositions to think and act a certain way) of which the clinician is generally not aware.

System 2 cognition is exemplified by the generation of a differential diagnosis list and examining the evidence for and against each diagnosis. System 2 utilizes explicit rules of logic; it is slow, effortful, entirely conscious, and analytical. Clinicians naturally favor the use of system 1 cognition because it is effortless. But the most effective clinical reasoning involves going back and forth iteratively between system 1 and system 2 cognition.

Now let’s return to the case vignette. The patient’s story is in your mind when you go into the waiting room. Depending upon your fund of knowledge and your experience, you might have what turns out to be an accurate diagnostic impression from the referral information. But perhaps you don’t. To get to the correct diagnosis, you might have to overcome the “framing effect” in which your cognition has been biased by the way the patient’s problem was first presented to you.

 In the case of Mr O, your intuition may have been biased toward thinking that the patient is depressed with somatic complaints precipitated by his recent retirement.

Now you escort the patient from the waiting room and by the time you and the patient have settled into the chairs in your office you have new information to include in your diagnostic formulation. Your system 1 cognition immediately registered that Mr O had parkinsonian features. His affect was somewhat flat and he walked slowly, with a diminished arm-swing.

Now you use system 2 logic in an effort to piece together the information you have so far. Does the narrative presentation fit with your observations? You interview the patient, carefully framing your questions to better understand the patient’s symptoms and the arc of his illness over time.

Knowledge and experience are both crucial in making the diagnosis of Parkinson disease in Mr O’s case. In addition to the blunting of facial expression and “feeling stiff and somewhat unsteady on his feet,” you learn that Mr O has been worried about falling, especially when he walks down a staircase. This is consistent with a shift in the center of gravity and forward propulsion associated with Parkinson disease.

Mr O also has had depression, prominent constipation, and fatigue-these symptoms are often prodromal in Parkinson disease, Lewy-body dementia, multiple systems atrophy and other, less common parkinsonian syndromes. If you know the symptoms for Parkinson disease, you ask Mr O whether his handwriting has gotten smaller. It has. Then you inquire about his sleep. He has had restless sleep for several years; on a number of occasions he has fallen out of bed. In addition, he has hit his wife in the middle of the night more than once, although he doesn’t remember doing this.

You might recognize that this is the classic presentation of rapid eye movement (REM) sleep behavior disorder, which is strongly associated with the subsequent development of Parkinson disease and related syndromes. In REM sleep behavior disorder, there is a failure of the usual inhibition of muscle tone that accompanies REM sleep. This allows the sleeper to move about during REM sleep and to act on dream content, including “fending off attackers” by lashing out.

To get to a correct diagnosis, clinicians must navigate a wide variety of inherent cognitive biases. For example, with Mr O, if you hadn’t realized from the referral that he might have had Parkinson disease, you had to overcome the impact of “anchoring,” the tendency to stick with your first diagnostic impression. You also had to overcome “availability bias,” the tendency to think that a diagnosis that readily comes to mind is likely to be the correct diagnosis.

For psychiatrists, major depression or dysthymia with somatic concerns is a diagnostic formulation that is commonly seen and readily comes to mind. Parkinson disease comes less readily to mind.

Cognitive biases are ubiquitous; they reflect the flow of nonconscious predictions we make, based on past experiences, as we move through the world. The influence of cognitive biases on diagnostic reasoning has been well described by Croskerry

 who has studied diagnostic errors in emergency department settings where physicians have to make quick decisions with little information about the patient and are forced to rely heavily on error-prone systems.

In the case of Mr O, it would have been a cognitive error to believe that the etiology of his symptoms was the difficulty he was having adjusting to retirement, along with his tendency to focus on somatic concerns. This would have been an “attribution error” in which you held the patient responsible for his or her disease. All physicians are prone to making attribution errors, especially when making a diagnosis in patients who have behavioral symptoms.

Another common bias is a tendency to look for confirming evidence-“confirmation bias”-rather than disconfirming evidence, although disconfirming evidence is much more powerful. It turns out that Mr O’s symptoms of restless sleep, constipation, fatigue, and depression actually began before he retired, not after.

Furthermore, it is helpful for clinicians to be aware of the possibility of “premature closure,” the tendency to stop investigating once you have come upon a diagnostic hypothesis but before that hypothesis has been fully proven. This is an especially easy error to make when a medical condition has a long prodromal period without symptoms that are specific enough to make a clear medical diagnosis. As psychiatrists, we often encounter diseases of this type; Parkinson disease is but one example. Others include: multiple sclerosis, Wilson disease, Alzheimer disease, Cushing disease, fronto-temporal dementia, Huntington disease, and more. Periodically reviewing a patient’s condition while maintaining diagnostic uncertainty forces the clinician to rely more on system 2 cognition.

Non-specific behavioral and mood alterations often represent the very first and, occasionally for prolonged periods of time, the one single and exclusive sign of an undetected physical illness. Flagrantly and convincingly “psychological” in nature on presentation, such masked physical conditions frequently mislead the examiner and obliterate any further medical consideration, resulting in misdiagnosis and thus, inevitably, in treatment gone astray.

Recent studies of diagnostic error have not focused on patients who are being treated in mental health clinics or inpatient psychiatric units; however, past studies of psychiatric patients found that, important medical diagnoses were missed in these patients as often as 40% of the time, depending upon the setting.

 Moreover, these medical diagnoses were not uncommonly the sole cause or a significant contributing factor to the patients’ presentations.

How can you contribute to decreasing diagnostic error rates? Expert opinion emphasizes: expand your knowledge; cultivate good clinical habits of mind, including expanding your knowledge and experience, self-care, humility, persistence, and the use of feedback; and utilize the use of metacognition-thinking about thinking, and work to improve the institutions within which you work.

There is much for psychiatrists to learn in the realm of neuropsychiatric disease. Often patients with medical conditions will first present to psychiatrists thinking they have a psychological problem or a mental illness. Many will have common diseases: focal seizure disorders; neurodegenerative diseases in addition to Parkinson disease, such as Alzheimer disease, vascular dementia, or Lewy-body dementia; the long-term consequences of traumatic brain injury; autoimmune diseases such as multiple sclerosis; or sleep disorders. Some patients will have diseases that are less common: anti-

-methyl-D-aspartate receptor encephalitis, Wilson disease, Huntington disease, frontotemporal dementia. Familiarize yourself with the clinical presentations of these and other neuropsychiatric conditions.

 And remember to keep this question in the front of your mind: Could this patient have a medical condition that I am missing?

Diagnosing is a high-level creative process; as such it relies on reflective practices that allow time for you to think about your reactions to patients and about your diagnostic process.

 Even with a few moments of mentally stepping back to get perspective are important. In addition, actively employ strategies that force you to use the conscious, analytic system 2 cognition. Ask yourself, “What could this be?” Make a differential diagnosis list. Work against premature closure in the face of doubt and uncertainty. Remember that keeping a diagnosis “open” forces your “problem-solving mind” to keep working on what the diagnosis might be.

Improving health care systems in support of diagnosing

Psychiatrists rely on hospital systems to support the diagnostic endeavor. Health care institutions may provide effective communication systems that allow collaboration with the patient and his or her family, health information technology, reliable laboratory services, access to library resources, expert second opinions, collaboration across disciplines, and specialties, and a culture that values reduction of diagnostic error rates while, at the same time, avoiding shaming and blaming.

Dr Schildkrout is Assistant Professor of Psychiatry, part time, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA. She is the author of two books:

 Unmasking Psychological Symptoms: How Therapists Can Learn to Recognize the Psychological Presentation of Medical Disorders 

 Masquerading Symptoms: Uncovering Physical Illnesses That Present as Psychological Problems.

. Washington, DC: National Academies Press; 2015.

 Croskerry P. The importance of cognitive errors in diagnosis and strategies to minimize them. 

 Croskerry P. Clinical cognition and diagnostic error: applications of a dual process model of reasoning. 

 Yates BL, Koran LM. Epidemiology and recognition of neuropsychiatric disorders in mental health settings. Ovsiew F, Ed. 

Neuropsychiatry and Mental Health Services

. Washington, DC: American Psychiatric Press; 1999: 23-67.

 Koranyi EK. Morbidity and rate of undiagnosed physical illness in a psychiatric clinic population. 

 Schildkrout B. Complexities of the diagnostic process. 

Masquerading Symptoms: Uncovering Physical Illnesses That Present as Psychological Problems

While the process of diagnosing is common to all fields of medicine, this article specifically addresses missed “medical” diagnoses in patients who present to or are being followed by psychiatrists and other mental health clinicians.

Diagnostic Errors in Neuropsychiatry

MyCopy [3], Printed eBook for just $24.99

In medical publishing, the casebook format has become increasingly popular-and for good reason. A memorable clinical vignette facilitates learning.

 As clinicians, we assimilate information best from case examples. We can imagine ourselves in the story, especially when the cases are drawn from real life and the authors do not edit out the confusions and uncertainties of actual psychiatric practice-the patient whose history is hard to follow; the individual with multiple diagnoses, or someone with an atypical presentation.

Pediatric Neuropsychiatry: A Case-Based Approach

 is a new casebook that focuses on the overlap of neurology and psychiatry in child practice.

 The co-editors, Aaron J. Hauptman and Jay A. Salpekar, two neuropsychiatry colleagues of mine, have called upon 65 contributing scholars to present a comprehensive, clinically relevant, and very readable text.

Psychiatrists are increasingly aware that the boundary between psychiatric disease and neurological disease is arbitrary.

 This book is written with the goal of presenting an integrated conceptualization of neurology/psychiatry and brain/behavior in the realm of pediatric neuropsychiatry practice.

Child and adolescent psychiatrists are on the front lines of neuropsychiatry. Everyday considerations in the practice of child and adolescent psychiatry include: brain development, genetic diseases, the influence of prenatal exposure to alcohol or drugs, nutritional influences on brain health, family dynamics, and educational opportunities that shape neurodevelopment. Many neuropsychiatric diseases that adult psychiatrists treat are first seen in children: autism spectrum disorders, ADHD, lead poisoning, fetal alcohol syndrome, sleep disorders, Tourette syndrome, epilepsy. 

 covers all of these topics and more-pediatric traumatic brain injury, anoxic brain injury, non-epileptic seizures, childhood multiple sclerosis, autoimmune limbic encephalitis, PANS [pediatric acute-onset neuropsychiatric syndrome] and PANDAS [pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection], hypothalamic tumors.

The book contains 26 chapters that focus on case examples. The case descriptions are followed by a discussion of diagnostic impressions, a succinct summary of the relevant neuroanatomy and pathophysiology, treatment strategies, and neuropsychiatric “lessons learned.” An additional chapter discusses the pediatric neuropsychiatric exam.

Throughout the book there are unique features such as: personal reflections written by patients or family members, “Clinical Pearls,” and summaries of educational materials or available resources like rating scales for ADHD. There is a substantial section on complementary and alternative medicine strategies for patients who have epilepsy. It is clear that the authors were writing with the needs of clinicians in mind.

While there are now 33 accredited fellowships open to psychiatrists who seek post-graduate training in Behavioral Neurology & Neuropsychiatry, no such formal programs are available in pediatric neuropsychiatry.

 For child and adolescent psychiatrists who are interested in learning more about neuropsychiatric thinking, this latest casebook is an excellent resource. There is also much material here that would appeal to psychiatrists with adult patients.

I spoke with Jay and Aaron about their book. Jay Salpekar is a Child and Adolescent Psychiatrist who runs a Neuropsychiatry in Epilepsy Program at Kennedy Krieger Institute, an institution specializing in brain and spinal cord diseases and developmental disabilities in children and young adults. He is also on the full-time neurology and psychiatry faculty at Johns Hopkins University School of Medicine.

When we first came up with the idea for this book, we knew that we wanted it to be different. We wanted to include patient and family stories and also their personal reflections; we think these are as important as the scientific background for enlightening our understanding of cases.

We were so gratified by the reception we got from chapter authors, all experts in their fields. We wanted cases that would illustrate brain and behavior relationships. It didn’t have to be the most rare case or a neat and tidy case. The contributors understood the concept and were totally on-board.

Aaron Hauptman is a Child and Adolescent Psychiatrist at Boston Children’s Hospital who is also in a Behavioral Neurology and Neuropsychiatry fellowship program at Brigham and Women’s Hospital. He works with individuals with developmental and acquired CNS injuries across the lifespan. According to Aaron,

In addition to providing accurate diagnoses, one of our main goals as clinicians is to be able to offer to the children and families who are struggling with neuropsychiatric illnesses an integrated formulation of their experiences. It’s not an either/or situation. And in fact, to try to pigeonhole what’s going on as either uniquely neurological or psychiatric is both invalidating and often inaccurate. A large part of why we wrote the book was to help give other clinicians a sense of this integrated approach.

A one-to-one correlation between brain and behavior is much less certain in children because they adapt so quickly. Despite the fact that prognostication and localization are so different for pediatric patients, still attention to neuroanatomical correlates of cognition, behavior, and emotion can be tremendously valuable.

In medical publishing, the casebook format has become increasingly popular-and for good reason. A new casebook focuses on the overlap of neurology and psychiatry in child practice.

Barbara Schildkrout, MD

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