Publisher Health

More than 20 of the birds, which are critically endangered, have died in recent months.The NewsFederal officials have granted emergency approval to a bird flu vaccine for use in California condors, an agency of the U.S. Department of Agriculture announced on Tuesday.The move comes after more than a dozen of the birds, which are critically endangered, recently died from the virus, known as H5N1. Worldwide, there are fewer than 600 California condors, which can have wingspans of nearly 10 feet. The emergency approval is “an attempt to prevent additional deaths of these birds,” said the agency, the Animal and Plant Health Inspection Service.It is not yet clear when California condors will begin getting vaccinated, but the endeavor will start with captive birds, said Dr. Carlos Sanchez, the head veterinarian at the Oregon Zoo, which has a condor breeding program and plans to vaccinate some of its birds. The condors will be closely monitored to make sure that the vaccine is safe and effective. “But as you can imagine, all this needs to happen fast so we don’t lose more birds,” he said.A California condor at the Los Angeles Zoo.Richard Vogel/Associated PressWhy It Matters: Condors are at high risk.The virus was first detected in a California condor found dead in late March. Since then, 20 more condors have died and four additional condors are currently in rehabilitation facilities, according to the federal agency. The virus has been confirmed in 15 of those birds.Condors appear to be “highly susceptible” to the virus, Dr. Sanchez said. “Once they get it,” he said, “they tend to have high mortality.”California condor populations dropped precipitously during the 20th century; in the 1980s, fewer than 30 birds were left. In the decades since, captive breeding programs have helped the population recover. If the virus gets into more condor populations, it could erase this progress, Dr. Sanchez said: “We’re talking about a potential catastrophic collapse of the conservation project.”Background: A new version of an old threat.The H5N1 virus was first detected in China in 1996. Since then, various versions of the virus have circulated in wild birds and caused repeated outbreaks in poultry. A new version of the virus arrived in North America in late 2021. Since then, it has spread rapidly throughout the United States, causing the largest bird flu outbreak in the nation’s history and resulting in the death of almost 60 million farmed birds.It has also taken a far heavier toll on wild birds than previous outbreaks. It has been detected in more than 6,700 wild birds — a figure that is surely an underestimate — in every state but Hawaii and has resulted in mass die-offs of wild birds around the world.It has also repeatedly spilled over into mammals and caused a small number of human infections, generally in people who were known to have been in close contact with birds. The virus is best adapted to birds, and the threat to the general public remains low, officials say. But scientists have long been concerned that the virus could evolve in ways that help it spread easily among people.What’s next: Officials are considering a broader bird vaccination campaign.The vaccine has been authorized for emergency use only in California condors. The small size of the existing California condor population will allow the vaccination program to be monitored closely, the Animal and Plant Health Inspection Service said. But the size and scope of the current outbreak have prompted officials to consider a mass poultry vaccination campaign. U.S.D.A. scientists have been testing numerous potential poultry vaccines and have said that some results could be available this spring.The country could see more animal outbreaks in the coming weeks as infected wild birds migrate north for the summer.

A new study adds to an emerging, radically new picture of how bacterial cells continually repair faulty sections of their DNA.
Published online May 16 in the journal Cell, the report describes the molecular mechanism behind a DNA repair pathway that counters the mistaken inclusion of a certain type of molecular building block, ribonucleotides, into genetic codes. Such mistakes are frequent in code-copying process in bacteria and other organisms. Given that ribonucleotide misincorporation can result in detrimental DNA code changes (mutations) and DNA breaks, all organisms have evolved to have a DNA repair pathway called ribonucleotide excision repair (RER) that quickly fixes such errors.
Last year a team led by Evgeny Nudler, PhD, the Julie Wilson Anderson Professor in the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, published two analyses of DNA repair in living E. coli cells. They found that most of the repair of certain types of DNA damage (bulky lesions), such as those caused by UV irradiation, can occur because damaged code sections have first been identified by a protein machine called RNA polymerase. RNA polymerase motors down the DNA chain, reading the code of DNA “letters” as it transcribes instructions into RNA molecules, which then direct protein building.
Nudler and coworkers found that during this transcription process, RNA polymerase also finds DNA lesions, and then serves as a platform for the assembly of a DNA repair machine called nucleotide excision repair (NER) complex. NER then snips out faulty DNA found and replaces it with an accurate copy. Without the action of RNA polymerase, little NER, if any, occurs in living bacteria.
Now the new study in Cell provides the first evidence that, like in the NER pathway, RER is tightly coupled to transcription. The study authors found evidence that the key enzyme involved in RER, RNaseHII, also cooperates with RNA polymerase as it scans for misincorporated ribonucleotides in the DNA chains of living bacterial cells.
“Our results continue to inspire a rethinking of certain basic principles in the DNA repair field,” says Nudler, also an investigator with the Howard Hughes Medical Institute. “Moving forward, our team plans to investigate whether RNA polymerase scans DNA for all kinds of problems and triggers repair genome-wide, not only in bacteria, but in human cells as well.”
Cutting Edge Techniques
Ribonucleotides (the building blocks of RNA) and deoxyribonucleotides (DNA components) are related compounds. As cells copy and build DNA chains in bacterial cells, they often mistakenly incorporate ribonucleotides into DNA chains in place of deoxyribonucleotides because they differ by only a single oxygen atom, say the study authors. In bacterial cells, DNA polymerase III is known to make about 2,000 of these mistakes every time it copies a cell’s genetic material. To maintain genome integrity, the bulk of misplaced ribonucleotides are removed by the RER pathway, but a key question had been about how RNaseHII finds relatively rare ribonucleotide lesions amidst an “ocean” of intact cellular DNA codes so quickly.
As they did in their 2022 studies, the researchers used quantitative mass spectrometry and in vivo protein-protein crosslinking to map the distances between chemically linked proteins, and so determined the key surfaces of RNaseHII and RNA polymerase as they interact in living bacterial cells. In this way they determined that most RNaseHII molecules couple with RNA polymerase.
In addition, they used cryogenic electron microscopy (CryoEM) to capture the high-resolution structures of RNaseHII bound to RNA polymerase to reveal the protein-protein interactions that define the RER complex. Further, structure-guided genetic experiments that weakened the RNA polymerase/RNaseHII interaction compromised RER.
“This work supports a model where RNaseHII scans DNA for misplaced ribonucleotides by riding on RNA polymerase while it moves along DNA,” says first study author Zhitai Hao, a post-doctoral scholar in Nudler’s lab. “This work is vital for our basic understanding of the DNA repair process and has far-reaching clinical implications.”
Along with Nudler and Hao, study authors in the Department of Biochemistry and Molecular Pharmacology the NYU Grossman School of University School of Medicine were Manjunath Gowder, Binod Bharati, Vitaly Epshtein, Vladimir Svetlov, and Ilya Shamovsky. The study was supported by the National Institute of Health, the Howard Hughes Medical Institute, and by the Blavatnik Family Foundation.

Two years of heavy exposure to TCE, a liquid chemical that lingers in the air, water and soil, may increase the risk of Parkinson’s disease by 70%.
Previous research has linked TCE, or trichloroethylene, to certain cancers, but a new study publishing in JAMA Neurology on May 15, 2023, is believed to be the first large-scale study to demonstrate its association with Parkinson’s.
TCE has been used for industrial and commercial purposes for nearly 100 years, and was used as a surgical anesthetic until it was banned in 1977. More recently it was used as a degreasing solvent. Today, it is primarily used to degrease industrial metal parts. This entails heating TCE in degreasing tanks to create a vapor that dissolves the grease, but it also releases the chemical into the atmosphere. Once TCE enters the soil or groundwater, it can persist for decades.
In the study, researchers led by UC San Francisco and the San Francisco VA Medical Center, compared Parkinson’s diagnoses in approximately 160,000 Navy and Marine veterans. Just over half came from Camp Lejeune in North Carolina, where TCE was used to degrease military equipment and water was contaminated; the remainder came from Camp Pendleton in California, where the water was not contaminated.
Service members spent at least three months in the camps between 1975 to 1985, a period when TCE in the water at Camp Lejeune exceeded maximum safety levels by 70-fold. The researchers had access to follow-up health data on the service members between 1997 and 2021, by which time Parkinson’s might be expected to develop.
Researchers found that 430 veterans had been diagnosed with Parkinson’s, and that the Lejeune veterans’ risk was 70% higher than the Pendleton veterans. On average, service members of both camps were stationed there approximately two years from 1975 to 1985. Residence began at an average age of 20, and Parkinson’s diagnosis occurred at an average age of 54 at Lejeune and 53 at Pendleton, showing that the disease took decades to develop after TCE exposure.

The civilian population is also at risk of TCE exposure, said first author Samuel M. Goldman, MD, MPH, of the UCSF Division of Occupational, Environmental and Climate Medicine, and the SFVA, noting that between 9% and 34% of U.S. water supplies contain measurable amounts of the chemical.
TCE Production Has Increased
“TCE is still a very commonly used chemical in the United States and throughout the world. Its production has been increasing over the past several years and it is widely available online,” he said.
“Unfortunately, there’s no easy way to know if you’ve been exposed, unless you’ve worked with it directly. Many of us have detectable levels of TCE in our bodies, but it gets metabolized and excreted very quickly, so blood and urine tests only reflect very recent exposure.”
Additionally, the researchers found that the Lejeune veterans had a higher prevalence of prodromal Parkinson’s — symptoms that are suggestive of Parkinson’s but do not yet fulfill diagnostic criteria for the disease.
“Loss of sense of smell, a sleep disorder known as RBD, anxiety, depression and constipation can be early signs of Parkinson’s, but only a very small fraction of people with them will develop it,” said senior author Caroline M. Tanner, MD, PhD, of the UCSF Department of Neurology, the Weill Institute for Neurosciences and the SFVA.
“The risk of developing Parkinson’s in the future can be estimated using a risk score based on these symptoms. The Lejeune veterans had higher risk scores than the Pendleton veterans, suggesting that they are more likely to develop Parkinson’s in the future.”

Watching the clock while trying to fall asleep exacerbates insomnia and the use of sleep aids, according to research from an Indiana University professor — and a small change could help people sleep better.
The research, led by Spencer Dawson, clinical assistant professor and associate director of clinical training in the College of Arts and Sciences’ Department of Psychological and Brain Sciences, focuses on a sample of nearly 5,000 patients presenting for care at a sleep clinic.
Insomnia affects between 4 and 22% of adults and is associated with long-term health problems including cardiovascular disease, diabetes and depression.
Participants completed questionnaires about the severity of their insomnia, their use of sleep medication and the time they spent monitoring their own behavior while trying to fall asleep. They were also asked to report any psychiatric diagnoses. Researchers conducted mediation analyses to determine how the factors influenced each other.
“We found time monitoring behavior mainly has an effect on sleep medication use because it exacerbates insomnia symptoms,” Dawson said. “People are concerned that they’re not getting enough sleep, then they start estimating how long it will take them to fall back asleep and when they have to be up. That is not the sort of activity that’s helpful in facilitating the ability to fall asleep — the more stressed out you are, the harder time you’re going to have falling asleep.”
As the frustration over sleeplessness grows, people are more likely to use sleep aids in an attempt to gain control over their sleep.
The results are published in The Primary Care Companion for CNS Disorders. Additional co-authors are Dr. Barry Krakow, professor of psychiatry and behavioral health in the Mercer University School of Medicine; Patricia Haynes, associate professor in the Mel and Enid Zuckerman School of Public Health at the University of Arizona and Darlynn Rojo-Wissar, a postdoctoral fellow at Alpert Medical School of Brown University.
Dawson said the research indicates a simple behavioral intervention could provide help for those struggling with insomnia. He gives the same advice to every new patient the first time they meet.
“One thing that people could do would be to turn around or cover up their clock, ditch the smart watch, get the phone away so they’re simply not checking the time,” Dawson said. “There’s not any place where watching the clock is particularly helpful.”
With 15 years of of research and clinical experience in the sleep field, Dawson is interested in comparing individuals’ sleeping experiences with what is concurrently happening in their brains. He trains and supervises doctoral students in the Department of Psychological and Brain Science’s Clinical Science Program.

The latest version of ChatGPT passed a radiology board-style exam, highlighting the potential of large language models but also revealing limitations that hinder reliability, according to two new research studies published in Radiology, a journal of the Radiological Society of North America (RSNA).
ChatGPT is an artificial intelligence (AI) chatbot that uses a deep learning model to recognize patterns and relationships between words in its vast training data to generate human-like responses based on a prompt. But since there is no source of truth in its training data, the tool can generate responses that are factually incorrect.
“The use of large language models like ChatGPT is exploding and only going to increase,” said lead author Rajesh Bhayana, M.D., FRCPC, an abdominal radiologist and technology lead at University Medical Imaging Toronto, Toronto General Hospital in Toronto, Canada. “Our research provides insight into ChatGPT’s performance in a radiology context, highlighting the incredible potential of large language models, along with the current limitations that make it unreliable.”
ChatGPT was recently named the fastest growing consumer application in history, and similar chatbots are being incorporated into popular search engines like Google and Bing that physicians and patients use to search for medical information, Dr. Bhayana noted.
To assess its performance on radiology board exam questions and explore strengths and limitations, Dr. Bhayana and colleagues first tested ChatGPT based on GPT-3.5, currently the most commonly used version. The researchers used 150 multiple-choice questions designed to match the style, content and difficulty of the Canadian Royal College and American Board of Radiology exams.
The questions did not include images and were grouped by question type to gain insight into performance: lower-order (knowledge recall, basic understanding) and higher-order (apply, analyze, synthesize) thinking. The higher-order thinking questions were further subclassified by type (description of imaging findings, clinical management, calculation and classification, disease associations).

The performance of ChatGPT was evaluated overall and by question type and topic. Confidence of language in responses was also assessed.
The researchers found that ChatGPT based on GPT-3.5 answered 69% of questions correctly (104 of 150), near the passing grade of 70% used by the Royal College in Canada. The model performed relatively well on questions requiring lower-order thinking (84%, 51 of 61), but struggled with questions involving higher-order thinking (60%, 53 of 89). More specifically, it struggled with higher-order questions involving description of imaging findings (61%, 28 of 46), calculation and classification (25%, 2 of 8), and application of concepts (30%, 3 of 10). Its poor performance on higher-order thinking questions was not surprising given its lack of radiology-specific pretraining.
GPT-4 was released in March 2023 in limited form to paid users, specifically claiming to have improved advanced reasoning capabilities over GPT-3.5.
In a follow-up study, GPT-4 answered 81% (121 of 150) of the same questions correctly, outperforming GPT-3.5 and exceeding the passing threshold of 70%. GPT-4 performed much better than GPT-3.5 on higher-order thinking questions (81%), more specifically those involving description of imaging findings (85%) and application of concepts (90%).
The findings suggest that GPT-4’s claimed improved advanced reasoning capabilities translate to enhanced performance in a radiology context. They also suggest improved contextual understanding of radiology-specific terminology, including imaging descriptions, which is critical to enable future downstream applications.

“Our study demonstrates an impressive improvement in performance of ChatGPT in radiology over a short time period, highlighting the growing potential of large language models in this context,” Dr. Bhayana said.
GPT-4 showed no improvement on lower-order thinking questions (80% vs 84%) and answered 12 questions incorrectly that GPT-3.5 answered correctly, raising questions related to its reliability for information gathering.
“We were initially surprised by ChatGPT’s accurate and confident answers to some challenging radiology questions, but then equally surprised by some very illogical and inaccurate assertions,” Dr. Bhayana said. “Of course, given how these models work, the inaccurate responses should not be particularly surprising.”
ChatGPT’s dangerous tendency to produce inaccurate responses, termed hallucinations, is less frequent in GPT-4 but still limits usability in medical education and practice at present.
Both studies showed that ChatGPT used confident language consistently, even when incorrect. This is particularly dangerous if solely relied on for information, Dr. Bhayana notes, especially for novices who may not recognize confident incorrect responses as inaccurate.
“To me, this is its biggest limitation. At present, ChatGPT is best used to spark ideas, help start the medical writing process and in data summarization. If used for quick information recall, it always needs to be fact-checked,” Dr. Bhayana said.

Inspired by sutures developed thousands of years ago, MIT engineers have designed “smart” sutures that can not only hold tissue in place, but also detect inflammation and release drugs.
The new sutures are derived from animal tissue, similar to the “catgut” sutures first used by the ancient Romans. In a modern twist, the MIT team coated the sutures with hydrogels that can be embedded with sensors, drugs, or even cells that release therapeutic molecules.
“What we have is a suture that is bioderived and modified with a hydrogel coating capable of being a reservoir for sensors for inflammation, or for drugs such as monoclonal antibodies to treat inflammation. Remarkably, the coating also has the capacity to retain cells that are viable for a prolonged period,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
The researchers envision that these sutures could help patients with Crohn’s disease heal after surgery to remove part of the intestine. The sutures could also be adapted for use to heal wounds or surgical incisions elsewhere in the body, the researchers say.
Former MIT postdocs Jung Seung Lee and Hyunjoon Kim are the lead authors of the paper, which appears today in the journal Matter.
Inspired by catgut
Catgut sutures — which are made from strands of purified collagen from cows, sheep, or goats (but not cats) — form strong knots that naturally dissolve within about 90 days. Although synthetic absorbable sutures are also available, catgut is still used in many types of surgery.

Traverso and his colleagues wanted to see if they could build on this type of tissue-derived suture to create a material that would be tough and absorbable, and have advanced functions such as sensing and drug delivery.
Such sutures could be particularly useful for Crohn’s disease patients who need to have a part of the intestine removed due to blockage from excessive scarring or inflammation. This procedure requires resealing the two ends left behind after one section of the intestine is removed. If that seal doesn’t hold tightly, it can lead to leaks that are dangerous for the patient.
To help reduce this risk, the MIT team wanted to design a suture that could not only hold the tissue in place but also detect inflammation, an early warning sign that the resealed intestines are not healing properly.
The researchers created their new sutures from pig tissue, which they “decellularized” using detergents, to reduce the chances of inducing inflammation in the host tissue. This process leaves behind a cell-free material that the researchers call “De-gut,” which contains structural proteins such as collagen, as well as other biomolecules found in the extracellular matrix that surrounds cells.
After dehydrating the tissue and twisting it into strands, the researchers evaluated its tensile strength — a measure of how much stretching it can withstand before breaking — and found that it was comparable to commercially available catgut sutures. They also found that the De-gut sutures induce much less of an immune response from surrounding tissue than traditional catgut.

“Decellularized tissues have been extensively used in regenerative medicine with their superb biofunctionality,” Lee says. “We now suggest a novel platform for performing sensing and delivery using decellularized tissue, which will open up new applications of tissue-derived materials.”
Smart applications
Next, the researchers set out to enhance the suture material with additional functions. To do that, they coated the sutures with a layer of hydrogel. Within the hydrogel, they can embed several types of cargo — microparticles that can sense inflammation, various drug molecules, or living cells.
For the sensor application, the researchers designed microparticles coated with peptides that are released when inflammation-associated enzymes called MMPs are present in the tissue. Those peptides can be detected using a simple urine test.
The researchers also showed that they could use the hydrogel coating to carry drugs that are used to treat inflammatory bowel disease, including a steroid called dexamethasone and a monoclonal antibody called adalimumab. These drugs were carried by microparticles made from FDA-approved polymers such as PLGA and PLA, which are used to control the release rate of drugs. This approach could also be adapted to deliver other kinds of drugs such as antibiotics or chemotherapy drugs, the researchers say.
These smart sutures could also be used to deliver therapeutic cells such as stem cells. To explore that possibility, the researchers embedded the sutures with stem cells engineered to express a fluorescent marker, and found that the cells remained viable for at least seven days when implanted in mice. The cells were also able to produce vascular endothelial growth factor (VEGF), a growth factor that stimulates blood cell growth.
The researchers are now working on further testing each of these possible applications, and on scaling up the manufacturing process for the sutures. They also hope to explore the possibility of using the sutures in parts of the body other than the gastrointestinal tract.
Other authors of the paper are Gwennyth Carroll, Gary Liu, Ameya Kirtane, Alison Hayward, Adam Wentworth, Aaron Lopes, Joy Collins, Siid Tamang, Keiko Ishida, Kaitlyn Hess, Junwei Li, and Sufeng Zhang.
The research was funded by the Leona M. and Harry B. Helmsley Charitable Trust, the MIT Department of Mechanical Engineering, the National Research Foundation of Korea, and a National Institute of Diabetes and Digestive and Kidney Disease Ruth L. Kirschstein NRSA Fellowship.

The deadly hospital pathogen Acinetobacter baumannii can live for a year on a hospital wall without food and water. Then, when it infects a vulnerable patient, it resists antibiotics as well as the body’s built-in infection-fighting response. The World Health Organization (WHO) recognises it as one of the three top pathogens in critical need of new antibiotic therapies.
Now, an international team, led by Macquarie University researchers Dr. Ram Maharjan and Associate Professor Amy Cain, have discovered how the superbug can survive harsh environments and then rebound, causing deadly infections. They have found a single protein that acts as a master regulator. When the protein is damaged, the bug loses its superpowers allowing it to be controlled, in a lab setting. The research is published in Nucleic Acids Research.
“We hope that our paper will encourage researchers worldwide to refocus on developing drugs to fight this superbug, which is spreading through the world’s hospitals, and killing already vulnerable people in intensive care units and other high-risk areas,” says Associate Professor Cain, the senior author on the paper.
There are six superbugs that scare global health officials. E. coli, Klebsiella pneumoniae and other gram-negative bacteria have common pathways that give them antibiotic resistance. A. baumannii is different. It’s particularly tough, and it’s one of the most resistant pathogens we encounter. Strangely, we don’t know much about how it infects us.
Breakthrough in a research challenge
“In the lab we can see this pathogen is very tough. Other researchers have shown that you can desiccate the bug for a year and when they added water, it was still able to infect mice,” says Associate Professor Cain.

“The problem had been that A. baumannii is relatively new on the scene, emerging as a problem in hospitals in the 1980s. And it’s hard to genetically manipulate with the existing molecular biology toolkit. It usually only infects sick people, but it is very resistant to antibiotics making it incredibly hard to treat and difficult to safely research. So, we don’t know much about it. We don’t know where it came from, nor how it became so resistant and resilient. Now, thanks to this paper, we know how it deals with stress.”
Amy and her colleagues realised about five years ago that they could make a difference by trying to understand the underlying biology of A. baumannii. That led to a major investment by Macquarie University in the research, in biocontainment laboratories for staff safety, and in an ethical animal model using moth caterpillars. The research effort has been strongly supported by the Australian Council and the National Health and Medical Research Council.
“We hope that our paper will encourage researchers worldwide to refocus on developing drugs to fight this superbug, which is spreading through the world’s hospitals.”
During infection our cells fight back by either flooding or starving bacteria of essential metals such as copper and zinc. A. baumannii has strong drug pumps that push antibiotics, metals and other threats out of the cell.
“By studying how this bug deals with infection stresses, we’ve found an important uncharacterised regulatory protein (DksA). When we disrupt this protein, it leads to changes in about 20 per cent of the bug’s genome and breaks its pumping system,” says Dr Ram Maharjan, a Macquarie University researcher and first author on the paper.
Not only does this protein control stress response, but it also controls virulence. A. baumannii usually spreads in blood but our disruption also caused it to be completely undetected in the blood of both Galleria mellonella and mice. It also becomes super sticky and harmlessly sticks to organs.
This has been a massive global research effort over the past five years, working with colleagues at Flinders University, Monash University, University of Cambridge, University of Wurzburg.

Listen to This ArticleAudio Recording by AudmIn my late 20s, living alone in New York, I found myself in the grip of a dark confusion, unclear of how to proceed — and so I started seeing a therapist. During most visits, I sat in a chair with a box of tissues on the small table beside it, but the office also held a couch, on which I occasionally reclined, staring at the ceiling as I wrestled with what I was doing with my life, and even what I was doing in that office. Back then, therapy was still perceived in some circles as a rarefied recourse for the irredeemably neurotic. I was embarrassed that I seemed to need it, and I could hardly afford the expense. It ate up so much of my pay that I sometimes daydream about the little house in the Catskills that I might now enjoy had I invested the money I spent on those twice-weekly sessions in any reputable mutual fund instead. Were they worth it? I know therapy provided me comfort, and I believe I developed some self-awareness, which has served me well. But during that phase of my life, I also spent more time than I should have, I’m sure, in a patently unhealthful relationship that my therapist and I endlessly discussed, as if it were a specimen to be dissected rather than discarded.Whatever my ambivalence about therapy, I trusted it enough to return to it several times, trying other modes that have become increasingly popular, including two versions of cognitive-behavioral therapy. More recently, I explored a form of therapy that had me locating my feelings in particular parts of my body so that I could — oh, I don’t know what, although I recall that I found it interesting at the time. Over the decades, and especially since the pandemic, the stigma of therapy has faded. It has come to be perceived as a form of important self-care, almost like a gym membership — normalized as a routine, healthful commitment, and clearly worth the many hours and sizable amounts of money invested. In 2021, 42 million adults in the United States sought mental-health care of one form or another, up from 27 million in 2002. Increasingly, Americans have bought into the idea that therapy is one way they can reliably and significantly better their lives. As I recently considered, once again, entering therapy, this time to adjust to some major life transitions, I tried to pinpoint how exactly it had (or had not) helped me in the past. That train of thought led me to wonder what research actually reveals about how effective talk therapy is in improving mental health. Occasionally I tried to raise the question with friends who were in therapy themselves, but they often seemed intent on changing the subject or even responded with a little hostility. I sensed that simply introducing the issue of research findings struck them as either threatening or irrelevant. What did some study matter in the face of the intangibles that enhanced their lives — a flash of insight, a new understanding of an irrational anger, a fresh recognition of another’s point of view? I, too, have no doubt that therapy can change people’s lives, and yet I still wanted to know how reliably it offers actual relief from suffering. Does therapy resolve the symptoms that cause so much pain — the feeling of dread in people who deal with anxiety, or insomnia in people who are depressed? Does the talking cure, in fact, cure? And if it does, how well? Sigmund Freud, the brilliant if dogmatic father of psychoanalysis, was famously uninterested in submitting his innovation to formal research, which he seemed to consider mere bean-counting in the face of his cerebral excavations of the unconscious. Presented with encouraging research that did emerge, Freud responded that he did not “put much value on these confirmations because the wealth of reliable observations on which these assertions rest make them independent of experimental verification.” A certain skepticism of the scientific method could be found in psychoanalytic circles well into the late 20th century, says Andrew Gerber, the president and medical director of a psychiatric treatment center in New Canaan, Conn., who pursued the use of neuroimaging to research the efficacy of therapy. “At my graduation from psychoanalytic training, a supervising analyst said to me, ‘Your analysis will cure you of the need to do research.’”Over time, formal psychoanalysis has largely given way to less-​libido-focused talk therapies, including psychodynamic therapy, a shorter-term practice that also focuses on habits and defenses developed earlier in life, and cognitive-behavioral therapy, which helps people learn to replace negative thought patterns with more positive ones. Hundreds of clinical trials have now been conducted on various forms of talk therapy, and on the whole, the vast body of research is quite clear: Talk therapy works, which is to say that people who undergo therapy have a higher chance of improving their mental health than those who do not. That conviction gained momentum in 1977, when the psychologists Mary Lee Smith and Gene V. Glass published the most statistically sophisticated analysis on the subject until that point. They looked at some 400 studies in a paper known as a meta-analysis — a term Glass coined — and found that among the “neurotics” and “psychotics” who had undergone various kinds of talk therapy, the typical patient fared better than 75 percent of those with similar diagnoses who went untreated. The finding that therapy has real benefits was replicated numerous times in subsequent years, in analyses applied to patients with anxiety, depression and other prevalent disorders.“I think the evidence is fairly clear that psychotherapy is remarkably effective,” says Bruce Wampold, a prominent researcher in the field who is an emeritus professor of counseling psychology at the University of Wisconsin-Madison. To him, the power of such a low-tech treatment is nothing short of miraculous, especially given that studies typically follow patients for 20 sessions or fewer: “The fact that you can just go talk to another human being — I mean, it’s more than just talking — and get effect sizes that are measurable, and remarkably large?” Wampold is best known for research suggesting that all types of evidence-based talk therapies work equally well, a controversial phenomenon known as the Dodo Bird effect. (The effect takes its name from the Dodo in “Alice’s Adventures in Wonderland,” who, when asked to judge a race, decrees, “Everybody has won, and all must have prizes!”) Hash out your childhood with a psychodynamic therapist, write down probabilities of feared outcomes with a cognitive-behavioral therapist, work on your boundaries with an interpersonal therapist — they will all yield equally positive results, found Wampold and others who have replicated his work. But there are reasons to think that this picture of therapy overpromises. As is true of much research, studies with less positive or striking results often go unpublished, so the body of scholarly work on therapy may show inflated effects. And researchers who look at different studies or choose different methods of data analysis have generated more conservative findings. Pim Cuijpers, a professor of clinical psychology at Vrije University in Amsterdam, co-wrote a 2021 meta-analysis confirming that therapy was effective in treating depression compared with controls, but he also found that more than half of the patients receiving therapy had little or no benefit and that only a third entered “remission” (meaning their symptoms lessened enough that they no longer met the study’s criteria for depression). Given that the patients were assessed just one to three months after treatment started, Cuijpers said he considered those results “a good success rate,” but he also noted that “more effective treatments are clearly needed” because so many patients did not meaningfully benefit. A blunter assessment of short-term therapies appears in a 2022 paper published by Falk Leichsenring and Christiane Steinert, psychotherapists and researchers affiliated with universities in Germany, who surveyed studies comprising some 650,000 patients suffering from a broad range of mental illnesses. “After more than half a century of research” and “millions of invested funds,” they wrote, the impact that therapy (and medication, for that matter) had on patients’ symptoms was “limited.”Such different interpretations of the data persist in part because of some of the field’s particular research challenges, starting with what constitutes a suitable control group. Many researchers put half the people who sign up to participate in a trial on a waiting list, in order to use that cohort as a control group. But critics of that method argue that languishing on a waiting list puts patients in an uncomfortable state of limbo, or makes them less likely to seek help from other sources, thus inflating the difference between their well-being and the well-being of those who received care. Other researchers try to provide a control group by offering a neutral nontherapy therapy, but even those are thought to have some placebo effect, which could make the effect of therapy look smaller than it really is. (One researcher, in trying to devise a neutral form of therapy to serve as a control, even managed to stumble on a practice that improved patients’ well-being about as well as established therapies.) So the debate continues, not just about the extent of therapy’s effectiveness but about the notion of the Dodo Bird effect. Many proponents of cognitive-behavioral therapy insist on the superiority of their approach for the treatment of depression and anxiety by pointing to competing meta-analyses. David Tolin, director of the Anxiety Disorders Center at the Institute of Living in Hartford, Conn., wrote one such meta-analysis. “Cognitive-behavioral therapy has a small to medium advantage over psychodynamic therapy,” he says. Nonetheless, he finds the measured results of cognitive-behavioral therapy to be unsatisfying, in his own research and in others’. He points to another meta-analysis of cognitive-behavioral therapy and anxiety disorders that found that only 50 percent of patients responded to the treatment. “It is not what I would call a home run,” he told me. Tolin has started to wonder if it’s time for research to shift away from talk therapy toward more innovative strategies. Leichsenring, too, has called for a “paradigm shift” in order to make further progress. For depression, there’s some evidence that therapy plus psychiatric medications is more effective than therapy or medication alone. Tolin believes that researchers should be focusing more attention on drugs that work in novel ways, such as one that has been shown to stimulate the same neurons that are active during cognitive-behavioral therapy. “Maybe we have reached the limit of what you can do by talking to somebody,” Tolin says. “Maybe it’s only going to get so good.” Illustration by Dadu ShinEllen Driessen is a psychologist in the Netherlands who believes, to the contrary, that the field has not yet unlocked the full potential of talk therapy. Driessen’s Twitter bio describes her as a “passionate depression treatment researcher,” and she has devoted herself in recent years to finding ways to maximize therapy’s effectiveness. Her goal: to determine which kinds of therapies work best for which kinds of patients, in the hope that those targeted pairings will yield better results. In her own practice, when patients turn to her for guidance about what treatment to choose, she often feels frustrated by uncertainty. The finding that all types of therapy work equally well, Driessen believes, could be hiding the variation that exists from person to person. Given the state of research, it is impossible to know what to recommend for an individual patient. “I don’t know which of these treatments will work best for you,” she resorts to saying. “And that is something that I, as a clinician, find very unsatisfying.”Most studies do not break down the results of various psychotherapies by type of patient — by gender, for example, or comorbidities, or age of onset of illness. The trials are too small to generate statistically meaningful results for those categories. Driessen and colleagues are undertaking the ambitious task of going back to the researchers on at least 100 trials to procure identifying details about patients, so that their samples will be large enough to allow them to determine whether certain kinds of people are more likely to respond to one kind of therapy or another. The project will most likely be underway for a decade before they can tease out matches between practice and patient. Another growing school of research, meanwhile, hopes to move practitioners away from adhering strictly to one school or another, by identifying the most effective components of each — the practice of exposing patients to the sources of their fears, for example, or examining relationship patterns. But Wampold believes that eventually these researchers will simply land, with their collection of techniques, on yet another form of therapy that proves about as effective as all the others. The most significant difference in patient outcomes, Wampold says, almost always lies in the skills of the therapist, rather than the techniques they rely on. Hundreds of studies have shown that the strength of the patient-therapist bond — a patient’s sense of safety and alignment with the therapist on how to reach defined goals — is a powerful predictor of how likely that patient is to experience results from therapy. But what distinguishes the therapists most likely to forge those bonds is not intuitive. Wampold says that some of the attributes that would seem most salient — a therapist’s agreeability, years of training, years of experience — do not correlate at all with effectiveness of care. To demonstrate the skills that do correlate, Timothy Anderson, director of the Psychology & Interpersonal Process Lab at Ohio University, studied groups of therapists who have been rated by patients as highly effective. He put them through a monitored exercise in which they were asked to respond to video clips featuring actors playing out difficult situations that commonly arise in therapy. “The patient might be saying, ‘This isn’t working — you can’t help me,’” Anderson says. He found that the highest-rated therapists tended, in those moments, to avoid responding with hostility or defensiveness, but instead replied with a pairing of language and tone that fostered a positive bond. “That’s displayed by the therapist saying things like, ‘We’re in this together,’” Anderson told me, “even when the patient is saying, ‘You can’t help me no matter what.’” Among the other qualities that these therapists displayed were verbal fluency — the ability to speak clearly in ways the patient could quickly grasp — along with an ability to persuade the patient and to focus on a specific problem. A certain humility in the face of the field’s uncertainties also seems to help; on a different questionnaire, therapists whose care was more successful gave responses that “reflected self-questioning about professional efficacy in treating clients.” For the past four years, Anderson says, he has been running workshops that aim to train therapists in these various skills. “Can we do it in brief workshops?” he says. “I’m not sure that we can.” Empathy, a capacity for alliance building — these might be innate, elusive, alchemic gifts that are challenging to teach. Anderson believes that people who become therapists tend to have more of those qualities than the general population, but he also referred to a study from the 1970s suggesting that laypeople who naturally have those skills performed nearly as well in therapeutic simulations as trained therapists with Ph.D.s. Is the idea, I asked Anderson, that patients should seek out therapists with whom they personally connect? That, just as most happy couples are made up of people who failed in previous relationships, the challenge lies in finding the right chemistry? Or is it more absolute? That perhaps some therapists are universally gifted at forging those bonds and can do so effectively with almost any patient. “They could both be true,” Anderson said. The answer struck me as yet another frustrating unknown in the field. I had perhaps — as a longtime consumer of therapy in search of reassurance — hit my limit with the disputes among the various clinicians and researchers, the caveats and the debates over methodology. “The research seems very … baggy,” I said, not bothering to hide my frustration. “It’s not very satisfying.” I could practically hear a smile on the other end of the phone. “Well, thank you,” Anderson said. “That’s what makes this research so interesting. That there are no simple answers, right?” A handful of well-chosen words — and I felt soothed, even touched by his positivity, which included, with that question mark at the end of his sentence, a hint of inclusiveness. Confronted with my clear annoyance, he had offered me a nondefensive, constructive and positive response. We were in this together. The exchange made me think of the best hours I have spent in therapy, times when I felt the depth of a therapist’s caring, or experienced the reframing of a particular thought that I hadn’t even known could be cast in so different a light. The therapist Stephen Mitchell has described therapy as a “shared effort to understand and make use of the pains and pleasures of life’s experiences.” Therapy, in his language, is not a practice that tries to fix any one thing, but one that aspires to help its participants build the most out of the challenges that face them. Jonathan Shedler, a psychodynamic psychologist and vocal critic of the research on therapy, believes that the field, in its narrow focus on reducing symptoms, fails to capture other ways patients benefit from psychodynamic therapy. “It’s not a fair comparison to look at how they’re doing the day therapy ends,” he says. “We’re aiming to go farther — to change something fundamental, so that people can feel more at peace with themselves and have more meaningful connections with others.”Anderson and I had set aside a half-hour to talk about therapist skills, and as the minutes passed, I felt that familiar sensation of the clock ticking, even as I wished he and I could keep talking — there was so much to discuss. Alas, he gently conveyed, our time was up.Dadu Shin is an illustrator in Brooklyn who has worked for clients like The New York Times and Armani Exchange. His work focuses on emotion and empathy.

Doctors quickly found the cause of the patient’s excruciating abdominal pain. They had to dig deeper to find what was giving him a peculiar tint.“You are so yellow,” the physician assistant told the 39-year-old man. It was said as a simple statement of fact. In the bright lights of the CityMD Urgent Care center in Ronkonkoma, N.Y., the man could see that this was true; his normally light brown skin now had a distinctly saffron cast to it. You need more than this walk-in center can offer, the P.A. explained. Stony Brook University Hospital wasn’t far away. Would he like her to call an ambulance for him?He could drive himself, he told her, although the thought of climbing back into his car and driving anywhere was unappealing. All he wanted to do was lie down and have someone tell him how he could make this terrible pain in his abdomen stop. Thank goodness for valet parking, he thought as he drove up to the emergency room. He left the key with the attendant and, holding his stomach, made his way to the crowded E.R.He had experienced pain like this in the past, though never this bad. Once or twice a year, he would eat something that didn’t seem to agree with him. He would feel bloated, his stomach tight and achy. Burping sometimes helped. But the pressure would get so bad that he would often make himself throw up to relieve it. The pain came in waves. He would feel a little pressure and know that more was coming. It would ease a bit and then hours later come roaring back, lasting longer. That would continue, each wave more intense than the last, for a day, sometimes two. And once the pressure started, he couldn’t eat. Anything more than water was brutal. Only when the pain stopped could he add broth or juice and build up from that.By the time he was called into the E.R. treatment area, his face and shirt were drenched with sweat. He could barely stand. Eventually he was helped onto a stretcher and placed in a cubicle. A half-dozen people came in, asked him questions, took his blood. He had a CT scan and an ultrasound, and within hours he had an answer: He had stones in his gallbladder. And one of them was stuck in the narrow tube that carries the digestive fluid known as bile from the gallbladder to the small intestine. That blockage was the source of the terrible pain. The stone would probably pass on its own — just as it did in all the painful episodes he had before. If not, it would have to be removed surgically. In any case, he was told, his gallbladder would be removed. He asked the many doctors he saw that night if this explained why he was so yellow. An unsatisfying “maybe” was all the answer he got.The Yellow MatterBy morning, the man was feeling better — the jammed gallstone must have gotten loose and moved on. He was sitting up in bed, reading his phone, when he noticed a small group of doctors collecting outside his door. A young woman gave what he recognized as a description of his own presentation to the emergency room. Then an older doctor began talking about jaundice, the yellowing of the skin and eyes. The color came from a buildup of something known as bilirubin, a breakdown product of red blood cells. Normally there is a constant low level of this dark-colored waste created and disposed of as red blood cells are born and die. But there are diseases that can increase bilirubin levels — either because something happens to block its excretion or because more red blood cells are being broken down, causing more bilirubin to be made. In this patient’s case, the stuck gallstone blocked the flow of bilirubin into the gastrointestinal tract. But that doesn’t usually cause jaundice like this. The whites of a patient’s eyes might be a little yellow — it’s where jaundice is most easily seen — but this man was visibly yellow everywhere. He had far more bilirubin than would be expected in a blocked gallbladder. Our job, he explained to the doctors in training, is to figure out why.“Do you think I’m hemolyzing?” the patient called out from his bed. Silence fell as every face turned toward him. Hemolyzing, they knew, was the destruction of red blood cells. But this wasn’t a word patients usually used. The patient got out of bed and ambled to the doorway. He could see the unasked question in their eyes. He went to medical school, he told the group, though he never went into practice.Dr. Peter Braverman introduced himself and the three doctors in training on the team. Here’s something else interesting, he told the patient and the trainees. If you look at the blood-cell count, you can see that this young man has an anemia — a lower-than-usual number of red blood cells. That’s rare in a man. And the blood cells he does have are very, very small. Usually you see that only with a severe iron deficiency or with some anomaly in the shape of the red blood cells. Normal ones are shaped like SweeTarts candies — disc-shaped, with an indentation on each side. That shape allows the cells maximal flexibility in order to move through the narrowest capillaries in the body. Red blood cells with any other shape are destroyed at a much higher rate. That can give you jaundice, especially if the elimination of the extra bilirubin is blocked. Let’s reach out to the hematology service, the doctor said, to help us figure out the mysteries of this man’s blood.Braverman, meanwhile, was curious. This young man had medical training. What did he make of his yellowed skin and eyes? The patient looked away uncomfortably. Actually, he hadn’t noticed it. During the pandemic, he moved in with his parents and was working from home. He had been quite isolated. Hadn’t been to his office. Hadn’t seen his friends. His parents, who were elderly, hadn’t said a word. And he didn’t look in the mirror much. In past years he noticed that the whites of his eyes sometimes had a yellow tint to them. Based on that, he had diagnosed himself with Gilbert’s syndrome, a benign condition that is caused by not having enough of the enzymes that break down bilirubin. People with Gilbert’s may have a yellowish cast to their eyes, especially during times of physical or emotional stress, when red blood cells are broken down more rapidly. But he never connected the yellow he sometimes saw in the mirror to the bouts of abdominal pains. And he had never been this yellow.Photo illustration by Ina JangStones and SludgeOver the next several days, the yellow in the patient’s skin and eyes faded. He was taken to the operating room. The gallbladder the surgeons removed was filled with dark brown stones and sludge — some of the excess bilirubin accumulated in the sac as pea-size accretions, and the rest continued to the intestines to be eliminated. It’s bilirubin that gives stool its dark color.While still in the hospital, the patient was seen by the hematology team. The small cells weren’t caused by a deficiency in iron. Indeed, he had plenty of iron. Instead, the specialists looked for some inherited abnormality in his red blood cells that caused them to be destroyed at a higher rate. He didn’t have sickle-cell disease. In this disorder, stress causes red blood cells to turn from SweeTarts to crescent moons that become trapped in the circulation and destroyed. Another common cause of the destruction of red blood cells is a deficiency of a protective enzyme called G6PD. Without this enzyme, infections, medications and even some foods can cause red blood cells to hemolyze. Thalassemia was a third possibility. Patients born with this inherited disorder make abnormal blood cells that are often destroyed at a much higher rate. Yet even before the patient left the hospital, his doctors knew he didn’t have any of these common inherited blood diseases.The patient saw the hematology team in its office several weeks later. The specialist sent off a half-dozen more tubes of blood, looking for some of the rare causes of hemolysis. This batch provided an answer: He had hereditary spherocytosis, a disease in which the red blood cells were tiny spheres rather than the usual biconcave discs. This shape makes them much easier to damage as they flow through narrowing blood vessels and other blood pathways, just as a fully inflated balloon is a lot easier to pop than one only half full.The patient asked how he could have inherited the disease. No one else in his very large family had it. Perhaps he was the first to have the mutation, the hematologist suggested. It wasn’t exactly the kind of first the man had imagined for himself. Still, he was glad to finally have an explanation for his episodes of abdominal pain. And really glad to know that now that he didn’t have a gallbladder, he wouldn’t have another.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.

Listen to This ArticleAudio Recording by AudmOne afternoon in 2020, early in the pandemic, I met Syl’violet and Matthew for a virtual session. Young, idealistic, deeply in love, they were also prone to dramatic fights. In this session Syl’violet, a vivacious essayist and spoken-word poet, was trying to describe the ways she felt Matthew, a measured medical student, was trying to control her, in this case by trying to dissuade her from buying a slushy. He thought they should keep to a tight budget until after he became a doctor and achieved financial stability. Then she could have “all the slushies you want later.” Syl’violet found his reasoning maddening, especially since he seemed to imply she was reckless.On the face of it, the fight seemed insignificant, but then an exchange took place that changed the tenor of the argument, connecting us to the underlying roots of the issue. “I have trouble envisioning that finish line,” Syl’violet exclaimed, tearing up, “because the plan that he’s talking about? My life has always been: The plan never works. You can do all the right things, you can obey all the right rules and get [expletive].” For a moment, Matthew continued to try to reason with her and convince her of his sound financial strategy. “I know that sounds very conceited, cocky,” he said, to which Syl’violet whipped back: “No! It sounds privileged!” She described her family’s relationship to money; they’d had nothing but trauma for generations. Syl’violet resented Matthew’s pride in his plan. “A privileged setting gave you access to all these things,” she said. “You’re taking ownership over it like, ‘I did it according to plan,’ as if, like, if other people did it according to plan, it would work out.”With the mention of the word “privilege,” Matthew came around to realizing they were talking about forces larger than themselves. Each of them was African American, but he came from a financially stable family; his parents, a firefighter and a bank manager, followed a middle-class trajectory and did well. “Let me rephrase,” Matthew said carefully, signaling to Syl’violet that he could see how his certainty about his future reflected his class background: “I recognize that if it wasn’t for my parents’ credit score, my loans to get — OK — so, I get that.” As the relevance of class and race came into focus, Syl’violet’s rage transformed into deep sorrow, generations of poverty weighing heavily on her. “I cannot stop thinking that we’re going to go bankrupt.” She worried that they might even be evicted. “I wish I could believe what you believe,” she told Matthew. He replied, his voice growing tender: “We have the same life now.” He looked at her, exuding care. “We have to live with the idea, the thinking, the viewpoint, that we’re going to die old together.”Syl’violet and MatthewDina Litovksy for The New York TimesOne of the most difficult challenges for couples is getting them to see beyond their own entrenched perspectives, to acknowledge a partner’s radical otherness and appreciate difference and sovereignty. People talk a good game about their efforts, but it’s quite a difficult psychological task. To be truly open to your partner’s experience, you must relinquish your conviction in the righteousness of your own position; this requires humility and the courage to tolerate uncertainty. Coming to see the working of implicit biases on us, grasping that our views are contingent on, let’s say, our gender, class background or skin color, is a humbling lesson. It pushes us beyond assuming sameness, opening up the possibility of seeing our partner’s point of view.I’ve been working as a psychologist seeing individuals and couples since the mid-1990s, and in the past eight years, I’ve witnessed a tremendous change in the kinds of conversations couples can have. Not long ago, if I would ask a couple about the ways class or race played out between them, I’d typically be met with an awkward shrug and a change of topic. But recent events have reshaped the national conversation on power, privilege, gender norms, whiteness and systemic racism. Together these ideas have pushed us to think, talk, argue and become aware of the many implicit biases we all carry about our identities, unconscious assumptions that privilege some and inflict harm on others. These insights have also made it easier for people to realize there may be plenty of other unconscious assumptions undergirding their positions. I’ve been surprised and excited by the impact of this new understanding, and it has all made my work as a couples therapist easier.There has, of course, been ferocious pushback against many of these ideas, claims that they are divisive or exclusionary. #MeToo, B.L.M. and trans rights have been weaponized in service of the culture wars dominating the media. But in my practice, I’ve found that engaging with these progressive movements has led to deep changes in our psyches. My patients, regardless of political affiliation, are incorporating the messages of social movements into the very structure of their being. New words make new thoughts and feelings possible. As a collective we appear to be coming around to the idea that bigger social forces run through us, animating us and pitting us against one another, whatever our conscious intentions. To invert a truism, the political is personal.Some five years ago I started working on a documentary series called “Couples Therapy,” created by the filmmakers Josh Kriegman, Elyse Steinberg and Eli Despres and airing on Showtime, that chronicles 18 to 20 weeks of therapy with couples who courageously volunteer to have their sessions filmed. (The couples in this essay were filmed for the show, which makes it possible for me to write about them; only some of those who are filmed end up on air.) We are now several seasons in. I was drawn to the project knowing that the directors were committed to an honest, vérité portrayal of therapy, and to looking at the social factors that thread through people’s lives and relationships.I am also trained as a psychoanalyst. Psychoanalysis is about exploring unconscious motivations behind thoughts or actions. It allows people to gain access to how early experiences — vicissitudes of attachment and trauma — have shaped them, and to expand their capacity for thought and feeling. For couples, I incorporate systems thinking, a practice that focuses on the system — a couple, say or a family — and interprets how each individual unconsciously behaves in ways that serve the system as a whole.But what we mean by “unconsciously” is an ongoing debate. Freud was known in the late 19th and early 20th centuries for his singular focus on the private, interior world. In particular, he wrote about the epic battle between unconscious drives and forces of civilization. Traditional psychoanalysis has mostly focused on early scenes between the young and their caregivers as shaping the psyche, leaving the sociopolitical context to other disciplines. I am of a later theoretical school that, rather than seeing civilization in conflict with the self, sees the social contract, our relationship to the collectives we belong to, as nested in the deepest corners of our unconscious. For me, psychoanalytic exploration is just as much about our deep ethical dilemmas regarding how to live with one another, and our environment, as it is about early family dramas; my patients’ repressed experiences with the ghosts of their country’s history are as interesting as with their mothers.Over the years, I’ve come to see that one of the most pernicious issues couples struggle with is working through wrongdoing and blame. The claim “You hurt me” often sends couples spiraling. People want to feel like good and lovable beings; their intentions make perfect sense to themselves, and they hate being interpreted as selfish. In psychoanalytic jargon we often say, “No one likes being the ‘bad object.’” In fact, there are few things people resist more than being held responsible for causing harm. It immediately threatens to overwhelm the “offender” with shame (Am I a bad person?) and guilt (Have I caused irreparable damage? Should I be punished?). Yet serious hurt that goes unacknowledged leads to the accumulation of resentment and a deadening of the relationship.Our ongoing national conversations about systemic biases have made it easier for couples to acknowledge wrongdoings by easing people into the idea of unconscious complicity. Accepting that you are part of a complex social system and implicated in its biases no matter what you tell yourself can also help you accept that in other aspects of your life, you are partly governed by unconscious forces you do not necessarily recognize. In Freudian terms, the ego is not a master in its own house. In other words, to know if you’ve caused harm, it is not enough to ask yourself, “Did I intend to hurt the other?”; you may need to listen to the feedback of others. These insights can have ripple effects beyond an awareness of specific biases, becoming relevant in many aspects of our lives — in our relationships with partners or children, in reviewing our life history. As my friend Nick described it: “Everything about me was raised to believe I am not racist or privileged, but in recent years I realize how easy certain things have always been for me simply because I’m white. I am humbled. And that has changed the way Rebecca and I talk with each other.”One of the most difficult challenges for couples is getting them to see beyond their own entrenched perspectives, to acknowledge a partner’s radical otherness.A shift in our vocabularies has also played a role. Language tends to evolve to better accommodate experiences of the dominant social group, leaving other experiences obscured from collective understanding, and thus silently perpetuating bias and harm. When these gaps are filled by new concepts, social change can follow. The expanding lexicon around bias and privilege includes terms like “white fragility” or “white tears,” referring to white people’s defensive refusal to fully engage with accountability; other phrases like “virtue signaling,” being “a Karen” or “performative allyship” underline the difference between honest and fake engagement with questions of ethics, morality and responsibility. These terms have implications beyond race, and I’ve seen them work their way into the therapy room. They’ve helped couples see the difference between the wish to receive forgiveness and assurance of your goodness and actual concern for the one you offended. Analysts call this distinction the difference between guilt and guiltiness. Guilt entails feeling bad for having harmed another; guiltiness is the preoccupation with yourself — whether you are or aren’t guilty. This preoccupation is all about warding off shame, which blocks concern for others.Questions of guilt hovered over another couple I worked with. He had recently cheated on his wife. They were generally deeply supportive of each other, but after she found out about his transgression, she was terribly upset and also confused. Their attempts to talk about what happened were halting. #MeToo rhetoric was woven into their discussions, functioning as a superego, shaping and inhibiting what they could even think. She said that she felt that the lessons of the movement were telling her not to forgive but to leave him — “Especially now, if a woman is being wronged, you get out.” It was hard for her to know how she actually felt about it all. Early on, he couldn’t separate remorse from fear. He was terrified of getting into trouble, and guiltiness prevailed. His voice was hushed while he scrutinized me intently, worried about how he would be perceived: “There are a lot of men in this business right now who have taken positions of power and use them to have sex with people.”They were both white and understood their privilege and were apologetic about it. She often undid her own complaints — “I levitate out” — by having the thought, “Oh, poor cis white woman.” He was uncomfortable, too. He talked about reading the news “about another Black or brown person being killed. And it’s just like I feel a little — well, I feel guilty, to be honest, to be sitting here.” The lessons of the Black Lives Matter movement initially can provoke such paralyzing guilt and shame that people become defensive and stop fully thinking. Yet over time, I’ve found, the ideas can inspire deep psychological work, pushing people to reckon with the harm that has been done, the question of whom should be implicated, and the difference between virtue signaling and deeper concerns. These are tough and important lessons that can carry over into intimate relationships. In this case, the husband described a new understanding about the ways he exercised power at work: “Hold on. Have I been an ally? Has it just been optics?” These insights extended even to his way of speaking about his transgression. He had been rationalizing his behavior by saying that his wife was not giving him the attention he needed. But moving beyond what the couple called “optics,” now he was asking himself for a more thorough accounting of what his cheating was really about, and how it affected his wife. He explained how lonely he was if she traveled; he felt left behind and discarded, a feeling deeply familiar to him from early childhood. Acknowledging his vulnerability was hard for him, but it opened up a series of honest conversations between them. “I convinced myself she does not desire me,” he said. “I’m not the popular guy. I’m not the strong guy.” He linked those feelings to insecurities he felt as a teenager, when he suffered chronic teasing from kids at school for being perceived as effeminate.This new, nondefensive way of talking made it possible for her to understand how his transgression hit her where she felt most insecure, and he could see it, generating remorse and forgiveness between them. She described how it had become easier for both of them to “check” themselves for their impact on the other person, and quickly “notice or apologize.” In one session she said, smiling: “You were a jerk to me yesterday, and then you apologized a couple hours later. You recognized that you took out your frustration there on me because I was an easy target.” He realized that he stopped skimming over ways he caused others pain: “I actually was just thinking therapy and the Black Lives Matter movement have made me keenly aware of the words that just came out of my mouth, and the understanding that she reacted adversely to that, instead of me just going, ‘We move on, because that’s awkward.’ There’s a need now to address it.” He continued: “ ‘Did I just upset you? What did I do to just upset you?’”Couples work always goes back to the challenge of otherness. Differences can show up around philosophical questions like what is important to devote a life to, or whether it is ethical to have babies with a climate crisis looming; or it can be closer to home, like whether having a sexual fantasy about a person who is not your partner is acceptable; or even as seemingly trivial as the correct way to load a dishwasher. Whatever the issue, differences can become a point of crisis in the relationship. Immediately the question of who is right, who gets their way or who has a better handle on reality pops up. Narcissistic vulnerabilities about self-worth appear, which then trigger an impulse to devalue the other. Partners try to resolve such impasses by digging in and working hard to convince the other of their own position, becoming further polarized.The challenge of otherness may be easiest to see when we think of racial differences. This was certainly true for James and Michelle. Michelle was a calm, gentle, somewhat reserved African American social worker, and James, at the time a police officer, was a slight, wiry white man whose face did not reveal much feeling. They came in with classic conflicts around division of labor and differing parenting styles, and then the pandemic hit. Quarantined, working remotely and home-schooling their 3-year-old son, they started fighting about Covid protocols. Michelle was aware of the way that Covid was devastating Black communities and wanted to be careful. James, along with his fellow police officers and his conservative parents, thought the concern was overblown. Discussion about how race shaped James and Michelle’s experiences and ideas routinely dead-ended. If Michelle tried to bring up the topic, James would insist, “I don’t see color,” and say he didn’t know what she was talking about. In our sessions, Michelle sounded hopeless: She wanted him to understand how traumatizing Covid had been for Black people. But she was frustrated by his inability to acknowledge real difference, as if everyone was the same race. “He’s of the mind-set that ‘I don’t see color.’” She continued setting out his thinking: “ ‘I don’t want to hear what you have to say because that’s not how I think.’” That point of view “obviously angers me,” she said. James would shrug, expressionless. Michelle was describing the infuriating experience of trying to break through a barrier: Her husband wasn’t consciously aware that whiteness was a perspective that was constricting what he could imagine or comprehend.After George Floyd was murdered and protests of all kinds erupted across the country, the dynamic between James and Michelle started to shift. Psychoanalysts are often interested in people’s fantasies, the scenarios running under the hood of conscious thought that express hidden desires and fears. When I asked James and Michelle about theirs, they shared apocalyptic ones: Each was imagining a full-on race war. Michelle imagined loss of all contact and trust between Black people and white people. James, who seemed uncharacteristically tense, saw himself on one side of a divide and was envisioning an “all-out physical combat.” “With whom?” I asked. “With anybody outside of this household. Anybody that tries to come and take anything from us because they’re struggling to survive and they start looting to feed their family, they’re now coming to my house.” Yet over time, as the conversation about Black lives continued, his own identifications became more complex and nuanced. He still felt loyalty to his fellow police officers and his conservative family, but he became aware that those feelings were now in tension with Michelle’s beliefs and what he was witnessing on the news about police violence against Black men and loud public demand for police reform.Michelle and James with their son.Dina Litovksy for The New York TimesJames’s changing internal landscape was reflected in his clear distress about “the all-out chaos that a large conflict can bring if we’re further divided in this country. You wouldn’t know who to trust from place to place.” Not knowing whom to trust also meant he could no longer trust his old belief system — in which it was clear who was “good” and who was “bad.” This disruption was creating new concerns and fantasies. Rather than fearing looters, he now feared polarization: “Michelle might be able to seek refuge somewhere where I might get shunned, or vice versa.” He was terrified that they wouldn’t be able to keep their young child safe.Interestingly, engaging with the question of systemic racism did not polarize Michelle and James but rather helped them do the important psychological work that I doubt I, as their therapist, could have inspired in them on my own. Something began to shift inside James, and he was no longer assuming sameness. He was no longer imposing his version of reality on Michelle, but rather “mentalizing” — understanding his and her mental states as separate and different subjective experiences: thoughts, feelings, beliefs and desires. In a meaningful moment he said, “I know it hits her harder than it does me.” I was moved to hear James plainly state: “We can never truly know what each other goes through because we’re not each other. So all we can do is be in as much understanding as possible.” He also recognized that he felt less defensive, “because she’s not directly attacking me.” And he saw a way for the two of them to remain connected, despite their difference. “We could get into a debate or an argument and be on opposite sides of the spectrum, completely juxtaposed, and manage to come through it and learn something about another perspective.”Michelle, who often described herself as guarded, also began to drop her defensive posture. She was looking at him fondly, her voice warmer. “These are things that I never really heard him fully articulate, particularly about his insecurities and feeling caught in the middle. That’s helpful for me to hear, because it makes me more conscious and aware of how he’s feeling.” For the first time, they were each entertaining multiple perspectives. Love is ultimately measured by people’s capacity to see and care about the other person as they are; succeeding in this effort is how people in relationships grow.Dr. Orna Guralnik is a clinical psychologist, a psychoanalyst and an academic who serves on the faculty of the N.Y.U. postdoctoral program in psychoanalysis, teaching a course in identity/politics and psychoanalysis with culture in mind. She is also the therapist on the Showtime documentary series “Couples Therapy.” Her writing centers on the intersection of psychoanalysis, dissociation and cultural studies. Dina Litovsky is a Ukrainian-born photographer who moved to New York in 1991. In 2020, she won the Nannen Prize, Germany’s foremost award for documentary photography.