is assistant professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Director of Community Psychiatry Clinics at the Harris Health System, Houston, Texas.

is Assistant Professor, Department of Psychiatry, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

 Tales From the Clinic: The Art of Psychiatry, 

we follow a psycho-oncology case of lung cancer, compounded by depressive and anxiety symptoms. Faced with fear of death, individuals go through stages of grief, as described by Elisabeth Kübler-Ross, MD, in 1969. This discussion highlights the psychotherapeutic, pharmacological, and diagnostic considerations of this comorbidity.

“Mr Arnold” is a 67-year-old retired teacher with no past psychiatric or medical history. He was referred to a psychiatry clinic for sadness and anxiety shortly after being diagnosed with metastatic adenocarcinoma of the lower lobe of the left lung. The devastating diagnosis caught Mr Arnold off guard just months into his retirement, as the only symptoms he experienced were cough and progressive fatigue. Besides these complaints, he had no past medical issues, always stayed committed to a healthy lifestyle, and underwent regular screenings and physical exams. Mr Arnold did not have any history of tobacco smoking, alcohol drinking, or any other substance use. He felt numb when he first heard the diagnosis because he was overwhelmed with a range of strong emotions: disbelief, anger, fear, anxiety, and sadness. Mr Arnold’s retirement plan now had to be put on hold so he could focus on cancer treatment. He had already suffered tremendous grief a few years earlier after the loss of his wife of 30 years to cancer. This time, he was traumatized by 

During the initial visit to the psychiatry clinic, he complained predominantly of fear of death, hopelessness, insomnia, social isolation, anger, guilt, and worry for his girlfriend if the treatment fails: “What will she do without me? Who will take care of her after I die?” Mirtazapine was started to target depression, anxiety, poor sleep, and low appetite; however, Mr Arnold found the medication too sedating. Sertraline was subsequently started and was much more tolerable and helpful with alleviation of anxiety and depression.

He was started on chemotherapy and radiation treatment soon after diagnosis. During the early stages of 

, he had difficulty coping with the treatment burden and reported worsening symptoms of anxiety. He was affected not only by the cancer diagnosis, but also by the treatment and its side effects, which worsened his depression and anxiety, lowered his quality of life, and exacerbated his loneliness and social isolation. Besides pharmacological intervention for depression and anxiety, he was concurrently seen by a psychotherapist to work on relaxation techniques, deep breathing exercises, and cognitive behavioral therapy. After persevering through almost 2 years of cancer treatment, Mr Arnold felt extremely relieved when the PET scan showed no evidence of active disease. Subsequent CT scans were negative as well. Mr Arnold later continued maintenance oral chemotherapy. While he felt relieved and hopeful for the future, a part of him still felt anxious that the cancer might recur.

Lung cancer is second only to breast cancer in prevalence. Older adults with lung cancer face a range of challenging issues, including demoralization, 

, treatment distress, anxiety, and depression. Some issues relate to loss of control and dignity, whereas others stem from problems related to quality of life. Smokers, or individuals who feel their cancer stemmed from negative behaviors of their own doing, often experience shame and worse depression.

 In therapy, fear of mortality and psychosocial decline need to be addressed. Stages of grief must also be highlighted and worked through, although stages do not have to occur in clean, predictable order.

For Mr Arnold, it was hard to imagine a worse time for him to receive the news of this devastating diagnosis because, after decades of working hard, he had been looking forward to spending the post-retirement years traveling. Like other patients, Mr Arnold found himself in shock (the denial/shock stages of grief). He now had to face the dreadful transition from anticipating years with joyful activities to navigating the uncharted waters of a deadly illness and difficult treatment. Mr Arnold experienced demoralization similar to Erik Erikson’s concept of despair in the final stage of one’s life, where he partially felt regret over the life he had lived and the feeling of 

Compared to other malignancies, lung cancer is associated with a higher rate of mortality and symptom burden, which can cause serious psychological suffering. Facing a terminal illness, Mr Arnold felt devastated and in despair; he now believed he had only a slim chance of being able to do the meaningful things that he had worked and planned for all his life (ie, traveling around the world). Although he reflected on the life he had lived with pride, having raised 2 successful children, he felt regret for not doing enough of what he felt would have brought him happiness (the depression stage of grief). During the course of his cancer treatment, Mr Arnold constantly found himself in a tug of war between hope for a full recovery (so he could travel) and, in his words, “make peace” (achieving ego integrity, the bargaining stage of 

) with the life that he had led and the fear of death.

Reflecting on his life, Mr Arnold felt that being diagnosed with lung cancer was unfair for him since he never had medical problems and had been committed to a healthy lifestyle (the anger stage of grief). He never smoked tobacco, drank alcohol, or abused any substance. Like most lung cancer patients, Mr Arnold was diagnosed when the cancer was in the late stage because his early symptoms—dry cough and fatigue—were nonspecific and dismissed without further work-up. He also reported feeling guilty about the possibility of becoming a burden on his girlfriend, who herself had chronic conditions. 

 is key in improving outcome at this stage in treatment.

 In aging patients, this is a common concern that needs to be addressed in multimodal treatment planning, as there is increasing recognition that caregiver health and patient health are interdependent.

During his first visit with psychiatry, Mr Arnold reiterated tearfully that he had saved money all his life for retirement and planned to travel extensively in the last meaningful years of his life. The addition of psychotherapy was essential in guiding the patient through the stages of grief. Although lung cancer is the most frequently occurring cancer and the leading cause of cancer death in men,

 it is essential to help patients realize that many cancer occurrences do not lead to death (the acceptance stage of grief). He was psychologically tormented by the 

, especially in the aftermath of the diagnosis and early stages of treatment.

As the lung cancer treatment progressed, Mr Arnold started to worry more about his financial situation since his retirement savings were quickly depleted by medical bills. He felt resentful that a significant portion of his retirement savings was now drained, and he could not help his girlfriend. Alleviating the burden of treatment in this situation was integral to improving the patient’s anxiety and depression. Considerations for patients in this situation include 

 of disease/cancer staging, likelihood of poor prognosis, and uncertainty in treatment and outcome.

Screening for depression among patients with lung cancer can be tricky as multiple confounding factors present as neurovegetative symptoms, mostly related to the cancer and its treatment; for example, low energy, poor appetite, decreased motivation, loss of interest, and decreased concentration. Research has shown that the level of distress experienced by lung cancer patients is not correlated with the type or stage of cancer, but that individuals with 

 may have higher health resource utilization and worse outcomes.

The best management of lung cancer and treatment distress requires early and comprehensive care coordination involving a multidisciplinary team to address physical suffering, spiritual needs, psychosocial stressors, nutritional needs, and psychological suffering. The goal is to provide adequate control of physical symptoms, psychosocial support, and management of anxiety and depression.

Another benefit of this antidepressant, and the reason it was selected as first line, is that it alleviates gastrointestinal symptoms (nausea) induced by chemotherapy and poor sleep related to distress and anxiety.

 for depression; the medication was also helpful for anxiety. Another benefit of this antidepressant, and the reason it was selected as first line, is that it alleviates gastrointestinal symptoms (nausea) induced by chemotherapy and poor sleep related to distress and anxiety. Mr Arnold had a good response to mirtazapine; however, the sedation caused by its side effect was a major issue because he already struggled with fatigue and low energy. Sertraline was later started and proved to be a better choice for his depressive symptoms. However, in treating patients with cancer, drug interactions have to carefully considered because selective serotonin reuptake inhibitors are sometimes associated with increased cytotoxicity when combined with certain chemotherapy agents.

Because of fatigue, depression, and anxiety, Mr Arnold notably lost interest in his routine activities. For the treatment of fatigue, he needed only conservative care such as physical therapy and energy conservation; no pharmacological intervention was required. During the course of 

, it was important to focus on Mr Arnold’s mood improvement based on depression symptoms that are psychologically based, rather than neurovegetative ones that are related to lung cancer such as fatigue, pain, dyspnea, weakness, insomnia, and poor concentration. Distinguishing physical symptoms due to cancer treatment is essential in this patient group.

The depression symptoms that were considered markers of depression response include feeling hopeless/helpless or unmotivated, easy crying, irritability, self-blaming, social isolation, and mood/affect change. The patient’s quality of life and other meaningful elements of his life were also important to consider when following up on the treatment of depression and anxiety. Helping the patient’s mood serves a dual purpose, both as a success in mental health treatment and a way to improve the patient’s immune system and improve adherence to the lengthy cancer treatment program. 

When evaluating anxiety among patients with lung cancer, it is also important to distinguish physiologically based dyspnea and anxiety from a psychological state.

Mr Arnold’s anxiety could have started with a respiratory deficit, but it was later exacerbated by the fear of death, catastrophizing, as well as feeling hopeless and helpless. Besides the psychological trauma, going through 20 months of radiation and chemotherapy was an ordeal for Mr Arnold, as he struggled with poor quality of life due to severe pain induced by the treatment. Because pain is a multidimensional and complex experience, it was imperative to explore the psychospiritual dimension of his suffering during follow-up visits. Discussing his pain, fear, concern, loss of autonomy, and dignity helped relieve Mr Arnold’s distress. Fortunately, he was not reluctant to talk about these concerns.

With a good response to the cancer treatment, Mr Arnold’s grieving mostly resolved after successfully completing his treatment, with residual intermittent anxiety of disease recurrence.

1. Siwik CJ, Phillips K, Zimmaro L, et al. 

Depressive symptoms among patients with lung cancer: elucidating the roles of shame, guilt, and self-compassion.

2. Ketcher D, Otto AK, Vadaparampil ST, et al. 

The psychosocial impact of spouse-caregiver chronic health conditions and personal history of cancer on well-being in patients with advanced cancer and their caregivers.

3. Bray F, Ferlay J, Soerjomataram I, et al. 

Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

4. Sullivan DR, Ganzini L, Duckart JP, et al. 

Treatment receipt and outcomes among lung cancer patients with depression.

5. Ester M, Culos-Reed SN, Abdul-Razzak A, et al. 

Feasibility of a multimodal exercise, nutrition, and palliative care intervention in advanced lung cancer.

The selective serotonin reuptake inhibitors enhance the cytotoxicity of sorafenib in hepatocellular carcinoma cells.

Comorbid depression in surgical cancer patients associated with non-routine discharge and readmission.

Articles

A patient, faced with a lung cancer diagnosis and the fear of death, goes through the stages of grief. How can you as clinicians lead them through?

“I’m Not Ready to Die”

The saying that “there is no free lunch” suggests that there are often mixed consequences for getting something for free. What seems free will always have hidden or implicit costs for someone.

Going Somewhere You’ve Never Been Before

Of course, literally speaking, free lunches have existed for a long time. The phrase may have originated in 19th century America saloons where free lunches were included as long as a drink was bought. Free lunches have been provided for basic nourishment in some schools with children from poor families.

Inside the Nation's Largest Guaranteed Income Experiment

,” there is a growing development in the country that can be used for a free lunch.

 Some variety of guaranteed income was a prominent feature of Andrew Yang’s presidential nomination run.

TIME started their story with the example of a poor family that had not experienced a sit-down meal at a restaurant in months. “It made me very happy,” said the mechanic recipient of a groundbreaking economic experiment called the Compton Pledge. He will receive $900 every 3 months for now.

A cynic could say that the restaurant meal was a frivolous way to spend some of that money, and if this is common, it will be a failed experiment. Psychologically speaking, it may have made the recipient and his family seem more valued. If so, that may be as valuable as the money itself.

is an award-winning psychiatrist who has specialized in the cultural and ethical aspects of psychiatry. A prolific writer and speaker, he received the one-time designation of Hero of Public Psychiatry from the Assembly of the American Psychiatric Association in 2002. He is an advocate for mental health issues relate to climate instability, burnout, Islamophobia, and anti-Semitism for a better world. He serves on the Editorial Board of

1. Vesoulis A, Abrams A. Inside the nation’s largest guaranteed income experiment. 

September 16, 2021. Accessed October 14, 2021. 

https://time.com/6097523/compton-universal-basic-income/

Is the saying “there is no free lunch” really true? 

The Psychological Value of a Free Lunch

This is a pop-up column. I write it soon after Blue Origin successfully completed its mission in its space journey of a few minutes with William Shatner, age 90, onboard. Of course, Shatner is associated with the original television series Star Trek, with its theme of “Where No Man Has Gone Before.” In this case, it was like life imitating art.

The Potluck of Columbus and Indigenous Peoples’ Day

I will leave it up to others to explain what this event meant for space explorations. Psychologically, though, here are some initial reactions.

Talk about new experiences! In some way, we have a new experience every moment and day of our lives. But something as different as this flight is so rare. Maybe even rarer is to have someone like Shatner describe it so poetically after he got off the capsule. Not only did he say that it was like nothing else he ever experienced, but that he never wanted to get over the experience. Research confirms that emotionally positive new experiences make us healthier and happier. We can look for them any time of our lives, including when we are 90.

Shatner also emphasized the thin blue “comforter” protecting our earth from the darkness of space. He hoped everyone could experience that. I took that to mean that if we did, we would be even more concerned about our deteriorating environment and climate. But at least we can vicariously relive his experience by watching the event and hearing him talk.

Maybe they will eventually want a mental health professional to go on a Blue Origin journey. If they do, let me know.

William Shatner, age 90, just made a brief journey to space—like life imitating art. 

Dr DeMossis an associate clinical professor in the Department of Psychiatry at The University of North Texas Health Science Center at Fort Worth in Texas.

Dr Elbasheeris a research coordinator in the Department of Behavioral Health Research at John Peter Smith Health Network in Fort Worth, Texas.

is a resident physician in the Department of Psychiatry at John Peter Smith Hospital.

is a pre-med Neuroscience student at the University of Texas at Austin.

FROM THE ACADEMY OF CONSULTATION-LIAISON PSYCHIATRY

This article is the second of a 3-part series that aims to highlight and review the prevalence, risk factors, clinical manifestations, diagnostic recommendations, proposed mechanisms of disease, and current treatment recommendations of folate, B

As reviewed in the previous article, key nutrients—or what Casimir Funk, PhD, termed vital amines—are essential to maintaining good health. Deficiencies in these key nutrients lead to certain pathognomonic disease states, as Funk initially observed when he fed birds a diet of only polished rice and they developed a diffuse polyneuritis (beriberi). Afterwards, the same birds were fed a diet of brown rice, and their “nervous symptoms rapidly disappeared.”

 What did this experiment establish? The importance of vital amines, or as we know them, 

Vitamins can be broadly delineated into 2 categories: water-soluble and fat-soluble. Water-soluble vitamins are absorbed rapidly via the gastrointestinal tract and distributed widely in various body tissues; however, as these vitamins are water-soluble, they are not efficiently stored in tissues. Therefore, these vitamins require regular consumption (either through diet or supplementation) to avoid deficiency states. Fat-soluble vitamins, on the other hand, are more easily stored, typically in adipose tissue, and require less frequent intake.

 Examples of water-soluble and fat-soluble vitamins can be found in 

 (cobalamin) is a water-soluble vitamin that is found in certain foods and is required for DNA synthesis and the formation of several hematologic elements, such as red blood cells (RBCs), white blood cells, and platelets.

 Individuals who have low levels of vitamin B

, due to either increased demand or poor absorption, are labeled vitamin B

 deficiency can lead to the formation of abnormal hematopoietic precursor cells such as megaloblastic RBCs, as seen in 

 deficiency is not only problematic for hematopoiesis; it also has severe neuropsychiatric consequences, including cognitive impairment, depression, 

, peripheral sensory deficits, and weakness. Lhermitte sign (

 can be tested by flexing the neck and assessing for shock-like sensations radiating to the feet. The mechanism is better understood for neuropathies (primarily dorsolateral myelopathy) associated with this deficiency as opposed to neuropsychiatric conditions. Most theories suggest that elevated methylmalonic acid (MMA) levels found in vitamin B

 deficiency may lead to demyelination of the peripheral nervous system and central nervous system.

 MMA accumulates in cells due to lack of vitamin B

 as a cofactor in the conversion of MMA to succinyl Co-A in cell metabolism.

There are several potential causes of vitamin B

 deficiency. Autoimmune pernicious anemia is the most common cause of vitamin B

 deficiency. Intrinsic factor (IF) and gastric parietal cells are attacked by gastric autoantibodies. IF is a glycoprotein that binds cobalamin and aids in the absorption of vitamin B

 in the terminal ileum. The depletion or lack of IF in pernicious anemia causes cobalamin deficiency.

 Other causes such as poor absorption related to pancreatic insufficiency, gastrectomy, intestinal surgeries, and inflammatory bowel disorders can also contribute to poor vitamin B

 absorption. Intestinal infections competing for vitamin B

 absorption such as small intestinal bacterial overgrowth or a parasitic infection should also be considered. 

 affecting absorption and transport of vitamin B

, such as transcobalamin deficiency, are currently being studied. Several medications can also lead to vitamin B

 deficiency via impaired absorption, metabolism, and utilization; these are listed in 

 Pure nutritional deficiency is usually only seen in strict vegans and is extremely rare.

Who Is at Highest Risk for This Disorder?

Some people are at more of an increased risk of vitamin B

 deficiency than others. Older adults are at increased risk of vitamin B

 deficiency due to gastric malabsorption secondary to gastric atrophy, chronic H. pylori infection, increased probability of gastric surgery history, and chronic use of medications like metformin and proton pump inhibitors.

 In patients with alcoholic liver disease, cobalamin levels may remain falsely elevated or normal despite low concentrations of liver tissue cobalamin and its active metabolites. This leads to a functional cobalamin deficiency. Proposed mechanisms of action include impaired uptake of serum cobalamin by the damaged liver, impaired storage of cobalamin in the liver that causes it to leak out, and reduced hepatic ability to synthesize transcobalamin. Vitamin B

 treatment has proven beneficial to some alcohol-dependent patients with megaloblastic anemia.

 Older adults, individuals taking the medications listed in 

 those with alcohol use disorders, pure vegans, and individuals with poor access to adequate nutrition (either through economic limitations or malabsorptive limitations) are at highest risk.

In 2008, the World Health Organization recommended vitamin B

 fortification standards in order to prevent deficiency in high-risk populations. Since then, some nations have implemented these strategies and are working to improve dosing standards. The United States has yet to implement mandatory vitamin B

 fortification, but certain foods, such as cereals, can be found to be fortified voluntarily.

When Should Screening and Prevention Be Done?

Screening and testing should occur in the following groups: those at high risk; individuals who have evidence of a macrocytosis or hyper-segmented neutrophils on peripheral blood smear; those with unexplained neurological conditions (eg, cognitive decline, weakness, ataxia, paresthesia); and those with unexplained psychosis and mood disturbances. Serum cobalamin levels are not always reliable in detecting vitamin B

 deficiency. If an asymptomatic high-risk patient presents with low to normal serum vitamin B

 levels, obtain serum homocysteine and MMA levels as a confirmatory test.

 If pernicious anemia is suspected, confirm the diagnosis by obtaining anti-IF antibody levels and serum gastrin/pepsinogen levels.

Those aged 50 years or older and strict vegetarians may benefit from vitamin B

 supplements or food fortified with vitamin B

, as the crystalline formulation is better absorbed than natural dietary cobalamin. Following gastric bypass surgery, patients should supplement with vitamin B

In the United States, older adults have the highest prevalence of vitamin B

 deficiency. In the United States and the United Kingdom, the prevalence of vitamin B

 deficiency was found to be 6% in adults 60 years of age or younger. In adults 60 years of age or older, the prevalence increases to 20%.

Patients exhibiting macrocytic anemia on initial complete blood count and peripheral blood smear should be evaluated for both folate and vitamin B

 deficiency, as these 2 conditions often present simultaneously. This can be done by assessing serum folate and B

 deficiency is usually made when serum levels are less than 111 pmol/L (150 pg/mL).

 Measurement of serum homocysteine and MMA can also aid in differentiating between folate and vitamin B

 deficiency, both homocysteine and MMA levels can be elevated.

 is the standard treatment. The cause of the deficiency will dictate how one administers the medication and how much to dose. Those with poor absorption, altered anatomy, and/or neurological/neuropsychiatric manifestations would likely benefit more from parenteral than from oral administration. Typical dosing for adults is 1000 mcg parenterally several times per week until the deficiency is corrected, then once per month.

 are both effective treatments for vitamin B

 is a key nutrient that is essential for our hematologic and neuropsychiatric functioning. With the prevalence of vitamin B

 deficiency reaching 20% in certain populations, it is crucial to recognize patients who are at risk and/or require treatment. Vitamin B

 replacement is relatively inexpensive and can be lifesaving when administered via the appropriate route and at the appropriate dosage.

 is an associate clinical professor in the Department of Psychiatry at the University of North Texas Health Science Center in Fort Worth, Texas.

is a research coordinator in the Department of Behavioral Health Research at John Peter Smith Health Network in Fort Worth, TX. 

is a resident physician in the Department of Psychiatry at John Peter Smith Hospital. 

 is a pre-med Neuroscience student at the University of Texas at Austin. Drs DeMoss, Elbasheer, Kunnel, and Mahi Raju report no conflicts of interest concerning the subject matter of this article.

1. Piro A, Tagarelli G, Lagonia P, et al. 

Casimir Funk: his discovery of the vitamins and their deficiency disorders.

3. National Center for Biotechnology Information. PubChem Compound Summary for CID 46853873, Cobalamin. Accessed August 26, 2021. 

https://pubchem.ncbi.nlm.nih.gov/compound/Cobalamin

5. Leishear K, Boudreau RM, Studenski SA, et al. 

 and sensory and motor peripheral nerve function in older adults.

6. Rodriguez NM, Shackelford K. Pernicious anemia. In: 

7. Busti AJ. Medications known to decrease vitamin B

 levels. Evidence-Based Medicine Consult. October 2015. Accessed August 26, 2021. 

https://www.ebmconsult.com/articles/vitamin-b12-medication-interactions-lower-levels

Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies

9. US Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference. Accessed August 26, 2021. 

https://www.ars.usda.gov/ARSUserFiles/80400535/DATA/sr21/sr21_doc.pdf

10. Andrès E, Loukili NH, Noel E, et al. 

 (cobalamin) deficiency in elderly patients. 

11. Fragasso A, Mannarella C, Ciancio A, Sacco A. 

 deficiency in alcoholics: an intriguing finding in a retrospective study of megaloblastic anemic patients

Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline

Key nutrients are essential to maintaining health. Here's an overview of B12. 

Exploring Vital Amines: The Who, What, When, Where, Why, and How of B12 Deficiency

is an assistant professor of psychiatry at the Feinstein Institutes for Medical Research and the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. She is the cofounder and chief science officer of North Shore Therapeutics.

One of my most memorable patients was a graduate student studying computer science. When I prompted her about her symptoms or medication adverse effects, I received staccato, unelaborated responses. But when I brought up programming, I found myself listening in fascinated confusion for minutes on end as she spoke about computer architecture, machine learning, and her views on 

—jumping from idea to idea and sometimes seeming to talk about multiple subjects at once. I frequently struggled to follow her thoughts, which were equal parts brilliant and bewildering. What if there were a way to turn this waterfall of words—which I could barely understand—into useful data?

Indeed, the words, phrases, sentences, and dialogues from our patients say so much. So does their breaths in between, and their voice and its dynamics, and the cadence and tonality used. These are the building blocks and foundations of our work as psychiatrists, whether we are an analyst in an armchair, dissecting and reconstructing a patient’s narrative, or a biological psychiatrist with pen in hand, translating the patient’s report into scales and delving for correlates in the brain. Although powerful and incisive, the most advanced methods of biological psychiatry—from neuroimaging and magnetoencephalography to induced pluripotent stem cells—are still far from overthrowing the primacy of patient reports. Syllable and sound are still the primary means for taking the measure of thoughts and emotions.

Speech and language disturbance have been recognized as core components of 

 since the fledgling days of modern psychiatry. In his canonical description of dementia praecox, which is often credited as the first modern characterization of schizophrenia, Emil Kraepelin, MD, described both positive (eg, incoherence, derailment, stereotypy, neologisms) and negative symptoms (eg, mutism) associated with speech (

 Writing Sample From Patientwith Schizophrenia

Moreover, it was observed that speech abnormalities in schizophrenia were not limited to content, but extended to prosody and vocal qualities: “The cadence often lacks the risings and fallings, the melodies of speech.”

 Kraepelin and others extrapolated these speech and language disturbances to indicate not only an impairment in communication, but also fundamentally disordered thought—at times derailment or loosening of associations, at times a poverty of thought.

Nancy Andreasen, MD, PhD, was among the first to formalize the assessment and measurement of thought disorder with her 1986 Scale for the Assessment of Thought Language and Communication (TLC).

 The TLC standardized definitions and provided anchors for clinician ratings of 18 items of speech disturbances, each focused on the content of speech. Items measure negative thought disorder (eg, poverty of speech, poverty of content of speech) and positive thought disorder (eg, derailment, pressure of speech, incoherence, etc). With the TLC and subsequent scales, Andreasen and other researchers were able to quantify speech disturbance in patients. They found that many features were shared with speech from patients in manic episodes, although mania was associated with greater positive thought disorder and 

Through advancements of machine learning and 

, we have new tools for taking the measure of speech and thought disturbance. Methods for extracting information from speech can be roughly divided into 2 areas. First, acoustics analysis extracts and quantifies information on pitch, amplitude, and vocal qualities on a millisecond-by-millisecond scale. Second, lexical analysis focuses on the content of speech, including word choice, grammar, the ideas being represented, and the relationship between words and ideas.

 The term “natural language processing” (NLP) describes computational approaches that use artificial intelligence to extract information from spoken or written language, or to produce naturalistic language.

 summarizes important measures produced by acoustic and lexical analyses and how they relate to clinical observations of speech disturbance in schizophrenia.

Acoustic and Lexical Measures in Relation to Speech Disturbance in Schizophrenia

Elvevåg and colleagues were the first to apply NLP to schizophrenia.

 In a 2007 study, they used latent semantic analysis to assign vector representations, like addresses for words, to speech content from individuals with schizophrenia. Elvevåg et al were able to quantify greater gaps across words in speech from patients with thought disorder, and compare those to gaps (if any) in individuals without the disorder. Clinically, these gaps can be interpreted as indicative of derailment or loosening of associations. This work presented a leap forward in our field: For the first time, scientists were able to objectively measure the space between thoughts.

Corcoran et al later used latent semantic analysis to show that reduced 

 (ie, greater leaps in content) predicted which youth at clinical risk for psychosis would later develop schizophrenia spectrum disorders and which would not.

 Rezaii et al accomplished the same goal by quantifying the density and richness of ideas conveyed in speech.

 Graph theory, which represents the relationships among words and corresponding ideas, was used by Mota et al to illustrate the loosely connected verbose speech of patients with mania as compared with the impoverished disconnected content of those with schizophrenia.

 Birnbaum et al applied NLP techniques to social media communication and found that word usage on 

 was able to predict subsequent rehospitalization.

Recently, my colleagues and I compared traditional clinical rating scales with NLP methods for differentiating speech in individuals with schizophrenia spectrum disorders from that of comparison participants without schizophrenia.

 The TLC scale was used to rate positive and negative thought disorder symptoms. Then, we used NLP methods to extract lexical information on multiple levels: individual words, parts of speech (eg, nouns, adverbs, adjectives, etc), and sentence-to-sentence coherence. When classifying participants into either the schizophrenia or health comparison group, we found machine learning algorithms performed significantly better using NLP-derived features (87% accuracy) than clinical ratings (68% accuracy), suggesting that important information is being captured by NLP. In addition, we found preliminary evidence that individuals with schizophrenia are much more likely to speak partial words (eg, “I went to th- the store” or “I guess we sho-… Let’s go out”), which has not been reported previously to our knowledge.

In another study, we combined acoustic and lexical speech features in machine learning models to predict separate items from the TLC.

 Importantly, we noted that speech disturbance in schizophrenia is likely multifaceted, and it should not be treated as a single uniform entity.

Based on their ability to measure thoughts in an automated, fast, objective, and inexpensive manner, speech biomarkers could fundamentally alter clinical psychiatric practice. As illustrated in 

, speech can be considered the visible extension of the changes in thought and brain circuitry that are at the core of schizophrenia. By mapping these connections, and leveraging the power of artificial intelligence and human language processing technology, I believe that we will develop a way to use language to scan the brain and offer personalized medicine.

 Speech Is the Observable Reflection of Underlying Disease Processes

Imagine a patient walking into an intake appointment and describing their experiences and circumstances. The psychiatrist hands the patient a tablet, which leads them through some brief speaking tasks. A spinning wheel appears for a few seconds, followed by numbers and graphs that reflect their symptoms and their related brain circuitry correlates. This brings up a menu that includes recommended 

, pharmacology, and psychotherapy, and offers ways to track progress and to warn of relapses before they occur. The scenario would not be very different from checking cancer markers in oncology, autoantibodies in rheumatology, or myriad existing paradigms in other medical fields.

Already, early evidence suggests that speech biomarkers reflect underlying changes in the brain. In work by Palaniyappan et al on the speech of individuals with mania or schizophrenia, decreased cohesiveness between concepts was significantly correlated with measures of resting state brain connectivity and gyrification (folding patterns of the brain).

 Perhaps, with additional research, we will be able to link specific speech markers to changes in specific circuits.

It is important to remember that our mission is the healing and well-being of individuals and families. This is not technology for the sake of novelty, no matter how nifty the gadget. Finally, the availability of brain measures should not mandate reliance on pharmacology over psychosocial interventions—quite the opposite. Automated language processing can be harnessed to measure changes in thought and brain structure on a personalized level. This layer of technology should not occlude the individual but rather allow clinicians to delve deeper into each unique case.

 is an assistant professor of psychiatry at the Feinstein Institutes for Medical Research and the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. She is the cofounder and chief science officer of North Shore Therapeutics. Disclosures: Dr Tang serves as a consultant for Winterlight Labs.

Scale for the assessment of thought, language, and communication (TLC). 

4. Cho S, Nevler N, Shellikeri S, et al. 

Lexical and acoustic characteristics of young and older healthy adults.

5. Corcoran CM, Mittal VA, Bearden CE, et al. 

Language as a biomarker for psychosis: a natural language processing approach.

6. Elvevåg B, Foltz PW, Weinberger DR, Goldberg TE. 

Quantifying incoherence in speech: an automated methodology and novel application to schizophrenia. 

7. Corcoran CM, Carrillo F, Fernández-Slezak D, et al. 

Syllable and sound are still the primary means for taking the measure of thoughts and emotions, the building blocks and foundations of psychiatric work. 

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