A child, not yet four years of age, scratches listlessly at the lesions on his legs and arms
Wed Feb 4 1998 – 00:00
A child, not yet four years of age, scratches listlessly at the lesions on his legs and arms. His father, eyes sunken in their sockets, sinks back in his crib. The boy’s mother is dead, taken by the virus, and her son will follow shortly.
Tinashe is an AIDS “orphan”, one of more than 500,000 children in Zimbabwe who have lost their mothers to the deadly disease. Worse, the virus was passed on in her blood and Tinashe too is infected.
Children are the saddest victims of this African holocaust, which is ripping the heart out of families throughout the continent. Shunned by their own society, which is so fearful of the new plague in its midst, their plight is also ignored by the West, which seems to have lost interest in AIDS.
On her regular visit to his oneroom home in Mbare, a slum district of Harare, Sister Eileen Clear blesses Tinashe with aroma therapy oil and prays with his father for his wellbeing. With her colleagues in the Mashambanzou Care Trust, she fights the disease with nothing stronger than a bottle of oil and a message of hope.
“In our view, the power of love and the power of affirmation can be stronger than AZT [the drug used in the West to treat HIV patients],” she says. “If people know they’re loved, they respond and their immune system responds.”
Nearby, the nuns run a creche for AIDS orphans. Smiling faces and full bellies cannot hide a mountain of tragedies. Twins Collettea and Colliwe are only three years of age, but have lost both their parents and live with their grandfather.
Tafadzwa still has her father, but he is deaf and dumb. “Her uncles were making a woman out of her – and they gave her the virus,” explains the co-ordinator, Ms Dorothy Abdul. Tafadzwa is four.
Up to three-quarters of these children will turn out to be HIV positive, but until they reach the age of 18 months, it is not possible to be certain that their mothers have infected them.
The nuns feed them well, and give them the love and attention they never get from their relatives. Those who make it to school go to the top of their classes.
“By taking good care of them, they become normal. But then the virus explodes when they start to get periods or sexual urges,” says Abdul. Few of those infected will live to be teenagers.
The spread of the epidemic has foisted parental duties on mere children. At Epworth, Sister Eileen visits Rumbi (16), who looks after four younger children in a single-room mud hut. Rumbi’s mother died of AIDS, as did an older, mentally-handicapped sister who was raped. Her father remarried, leaving his first family to tend for itself.
Just being a teenager is a trauma in itself. But Rumbi is missing school because of her duties, and she has to cope with the sneers of neighbours.
“They look down on us because we need welfare,” she tells Sister Eileen, tears streaming down her face.
Back at the Mashambanzou care centre, a 24-year-old woman has died during the night. A nine-year-old girl, the victim of a rape, is admitted. The local staff who care for the sufferers are HIV positive themselves.
The centre was founded by two Irish nuns of the Little Company of Mary, who had grown tired of tending to the wealthy in a private hospital in Harare. The nuns have cobbled together financial support from a variety of donors to bring succour to AIDS sufferers. The then president, Mrs Mary Robinson, visited them in 1994, and Princess Diana also came on a private visit.
Sister Noreen Nolan acknowledges their work is “only a drop in the ocean”. The death toll from AIDS in Zimbabwe is the equivalent of four large plane crashes every week.
The disease has cut a swathe through all areas of life. Coffinmakers are short of wood; employers are losing workers. Many of those affected are young and highly qualified, and their deaths are an incalculable loss to the economy.
An Irish civil engineer tells me four of his colleagues have died of AIDS in the past year: “They’re at their desks one day, and gone the next. No-one speaks about what happened to them.”
Official figures show that life expectancy in Zimbabwe has dropped from 61 years in 1990 to only 49 years today. A further drop, to 30 years, is predicted.
Decades of investment and development have been wiped out as AIDS patients overburden the health system. Eighty per cent of hospital beds are occupied by sufferers, and 20 per cent of health spending goes on terminal care for their last year of life.
Zimbabwe’s tragedy is being repeated in most states in sub-Saharan Africa. As the incidence of HIV and AIDS drops in western countries, Africa accounts for 20 million out of a total of 30 million cases worldwide.
AIDS is now mainly a poor person’s disease, like malaria. And as in the case of malaria, the poor in Africa will have to wait a long time for the West to find a cheap cure. New drug cocktails have been developed to extend the life of wealthy HIV sufferers in the West, but these cost £10,000 per patient per year. Many developing countries spend less than £5 per patient per year.
Everywhere, prevention is better than cure. In Africa, prevention is the only solution. Zimbabwe has managed to cut by half the level of sexually-transmitted diseases among miners and in the army by distributing free condoms. In stores, “Protector”, the most common brand of condom, is sold openly alongside school jotters and pencils.
But educating for change in a culture of male permissiveness and female acceptance will not be easy. Sister Noreen believes that AIDS is a social problem, not a health one. Tackling the disease means tackling the social circumstances, such as poverty and overcrowding, in which the disease thrives.
Lifeskills programmes for schools which were developed by Unicef and funded by Irish Aid are explicit about the dangers of unprotected sex.
But cultural habits die hard. Men are unwilling to use condoms. As one worker reports: “They say it’s like eating a sweet with the paper on.”
For more than 25 years, Richard Youins struggled to find help with his drug addiction. Youins is from New Haven, Conn., home to both Yale University and a number of less affluent neighborhoods—his community has been shaken by murders and drug-related crimes during the pandemic. Substance use clinics and treatment sites were available, but he felt the care they provided overlooked who he was as a person. The needs “of our community weren’t being addressed,” says Youins, who is Black. “It wasn’t realistic.”
Youins felt that traditional mental health care ignores the social, economic, emotional and faith-based needs of underserved communities. “After hanging out and spending all my money on a Saturday night, I would feel so ashamed I wanted to go and talk to God,” but doing so felt out of reach because he felt unwelcome in church settings, and the services available to him did not cultivate that type of much needed support network, he says. Now sober, Youins works as a peer-support specialist with the Connecticut Mental Health Center and has seen how COVID worsened mental health challenges in his city. “It’s a trying time,” he says.
Rates of mental illness were already high in the U.S., but the pandemic intensified everything: Illness, loneliness, job loss, grief, and other stressors related to COVID induced a nationwide rise in anxiety and depression. As difficult as the pandemic has been, however, it hit some groups far harder than others. It exacerbated social and economic inequities already known to drive and sustain poor mental health among marginalized communities. Those in rural America, already less likely to receive mental health care than those in urban areas, were particularly hard hit. So were people of color, who are more likely to be hospitalized and die from COVID and are less likely to receive mental health care compared with white people. And for those who were unhoused or formerly incarcerated, the consequences have been profound.
Madhuri Jha, director of the Kennedy-Satcher Center for Mental Health Equity at the Morehouse School of Medicine, witnessed how COVID impacted unhoused people with serious mental illness when she led a mobile behavioral health unit in New York City early in the pandemic. “It wasn’t just death” that increased when the pandemic hit, she says. “It was accidental overdose, suicide, incarceration. It was people going missing and no way to account for it.”
Now experts in the mental health field are acknowledging that they must confront ugly truths in the American health-care system, including structural racism and classism. “The pandemic has caused universal harm to everybody’s mental health, but for people who are most vulnerable, for people who are most traditionally oppressed and marginalized, that harm becomes greater and more significant,” says Ruth Shim, who researches equitable approaches to mental health care as director of cultural psychiatry at the University of California, Davis.
The pandemic was an urgent wake-up call for providers, community stakeholders and politicians, prompting them to reimagine mental health care and delivery. Shim and others are looking at how they can improve equity. What they are finding is that, to succeed in underserved communities, they need solutions that foster a sense of belonging. These include expanding access to care, improving research on community mental health and empowering people to tackle their own problems.
Combining these efforts leads to the most robust and long-lasting response, says Helena Hansen, associate director of the Center for Social Medicine at U.C.L.A.’s David Geffen School of Medicine. All efforts, she says, must be built on the understanding that issues such as racism and classism drive social determinants of mental health, such as unstable housing or lack of insurance. “The way our system is set up now is deliberately crafted to exclude certain people,” Hansen says. “If we want to address social determinants that provide a sense of connection to others, which is really the heart of mental health recovery, we have to rethink what mental health care looks like.”
Gaining Access to Care
During his addiction, Youins learned that just because mental health care services existed did not mean they were accessible. Although equal access to mental health care is broadly acknowledged as a civil right, many still struggle to get it. One major reason is cost: Not only is it expensive but many mental health practitioners do not accept insurance, let alone Medicaid, because insurance companies do not compensate them adequately. People who are most likely to be in therapy are those who can pay out of pocket.
The obvious solution to expanding access in the U.S., Shim says, is establishing universal health care, which would assure coverage regardless of someone’s ability to pay. Until that happens, however, mental health organizations that are designed by and serve marginalized communities can play a meaningful role in overcoming cost-related and social factors that reduce access to care. “We need to be at the table, making decisions,” Youins says.
Some groups have emerged to do exactly that. One of the mental health equity projects Youins works with is Imani Breakthrough, a free, New Haven–based recovery program designed to help Black and Latinx people overcome drug and alcohol use disorders within a church setting. Another group called the Asian Mental Health Collective (AMHC), which formed partly in response to the rise in anti-Asian violence during the pandemic, connects 30 people per quarter to eight free sessions of therapy with an Asian American provider through its subsidized therapy program.
In addition to cost, another factor that might prevent people from seeking care is stigma around mental illness. By confronting and dismantling negative stereotypes about mental health, organizations such as the AMHC and another group, called Rural Minds, aim to expand access to care in their communities.
Jeff Winton founded Rural Minds after his 28-year-old nephew, who worked on the family dairy farm in upstate New York, died from suicide. Neighbors suggested Winton tell people that the death was the result of natural causes. In rural areas, Winton explains, “mental health is not considered an illness; it’s considered a character flaw.” Instead of covering up the suicide, he spoke about his nephew’s struggles in his eulogy. Afterward, people lined up to share their own experiences with mental illness.
In rural America, stigma is hardly the only issue: even when people want care, they often cannot find a therapist. As of March 2022, more than 35 million Americans in rural areas lacked access to a mental health provider.
One solution that has shown promise is telehealth, which exploded in popularity during the pandemic. Pravesh Sharma, a pediatric psychiatrist in Eau Claire, Wis., says the technology has enabled him to talk with patients who would otherwise have to travel for hours to reach his clinic. Now up to 40 percent of his practice is made up of telehealth appointments. Such a call allowed him to connect with a transgender patient in a rural area who needed support communicating with their conservative family. After their calls, Sharma says, the client was better able to have conversations with their family and community.
Telehealth’s primary drawback is, yet again, access. It’s useless when someone lacks an Internet connection, a private place from which to call, a computer or mobile phone, or the ability to navigate a digital environment—all common issues for people in poor communities and communities of color.
The Heart of the Problem
Growing up near Yale, Youins noticed that a number of the university’s mental health studies were focused on the city’s Black population, but his community rarely saw any lasting impacts. “People come in and do a lot of research, but they don’t share that information. They use us as guinea pigs,” he says. Because the projects would come and go, “you can’t even measure if they really work.”
Researchers agree that to focus on the inequities of marginalized groups, it is critical to gather data on their experiences. “People in Congress do not see a problem when there [are] no data,” Jha says. But a data set is useless if it is not collected in a culturally sensitive way, and current research tools are not always sensitive enough to gather information about nonwhite populations. Non-English speakers, for example, are usually not represented in mental health data, because they do not understand survey questions, Jha says. Furthermore, because people self-identify in a number of ways, racial and ethnic demographics can be difficult to capture.
Historically biased systems also mean measurements of suffering among certain racial and ethnic minority groups can be inaccurate. Mental health stigma prevents people from seeking care and reporting symptoms in the first place. Even when they do, they are often misdiagnosed as a result of longtime racialized diagnostic biases, which the psychiatric community has only now begun to address. For instance, studies show that Black Americans are more likely to be misdiagnosed with schizophrenia than white Americans.
Another issue with data collection on disparities is that most efforts focus on measuring a community’s deficiencies rather than its strengths, Jha says, which leaves “no pathway to actually understanding what the solutions are.” For example, a study might focus on measuring how many people of color have a serious mental illness but not their ability to withstand and adapt to the challenges their condition poses.
Ultimately good data are useful only when applied effectively and appropriately. For research to translate into something that serves the people it is about, Shim says, it must involve them throughout the scientific process, from conceptualization of the study to dissemination of the results. And a share of the funding, which often comes from government grants and may amount to millions of dollars, should go toward supporting the communities that the research is focused on. “The very communities that they’re studying don’t see any of that investment at all,” Shim says.
Community Healing
Allowing communities to be engaged in their own care may be the most important step toward achieving mental health equity. “When a community is empowered to solve their own problems, they’re often very effective,” Shim says.
Imani Breakthrough, where Youins is a peer coach, has been recognized as a successful model for community mental health support. Co-developed by psychiatry researchers Ayana Jordan of New York University and Chyrell Bellamy of Yale University, the program offers classes, provided in a church setting, to promote wellness and recovery. Sessions are led by people from the local Black and Latinx communities—usually a member of the church and a coach who has lived with substance use. “The person sitting on the other side of the table looks like me, knows about me and knows we have similar things in common,” Youins says. This familiarity helps people in the program overcome hesitancy in seeking care that often stems from discrimination they may face at traditional clinics. Holding classes in a church, which has cultural significance, fosters a comfortable and welcoming environment.
Another successful model is Crisis Assistance Helping Out On The Streets (CAHOOTS), a mobile mental health crisis intervention program in Eugene and Springfield, Ore., that is more than 30 years old. CAHOOTS diverts mental health–related crisis calls away from the police and toward its own team of trained specialists, who handle crises without weapons or law enforcement. Funded by the Eugene and Springfield police departments, it mostly serves people marginalized by racism, classism and ableism, people who are typically wary of police-led crisis responses, which often result in arrest or even death.
CAHOOTS is staffed largely by survivors of mental health crises like Daniel Felts, who has worked for the organization as an EMT and crisis worker for five years. When Felts attempted suicide at age 19, six police officers with guns showed up. He was a danger to himself, he says, “But then I became distinctly aware that these folks could take my life if I made the wrong move.”
Felts later joined CAHOOTS because it provided a nonviolent, unarmed response to mental health crisis calls, did not bill its patients and prioritized comprehensive care—everything from medical aid to connecting people to food and shelter. It aims to “meet people where they are and be sensitive to the intersectionality of our patient population,” Felts says.
Providers Also Need Support
Administering equitable mental health care comes with a cost: provider burnout. A survey of more than 20,000 health-care workers between May and October 2020 found that 49 percent had burnout and 43 percent suffered from work overload. Providers who are Black, Indigenous and people of color (BIPOC) caring for their own disproportionately affected communities are among the hardest hit. During the pandemic, female, Black and Latinx workers have reported higher stress levels than their male and white counterparts.
“There’s a certain urgency in mental health care,” Hansen says. A growing number of psychiatrists and therapists are reporting burnout, and a record number are leaving clinical practice. Even at a community-led group like CAHOOTS, COVID-related setbacks made it difficult to retain burned-out staff, Felts says.
Jessica Dominguez, founder and lead clinician of La Clínica, a program offering culturally sensitive mental health therapy to Latinx patients at a Kaiser Permanente center in California, says she has seen more BIPOC clinicians leave the company during COVID than ever because they felt undervalued. With fewer Spanish-speaking and other bilingual clinicians available, non-English-speaking patients have wait times that are much longer compared with those of their English-speaking counterparts.
In October 2021 Dominguez and other mental health clinicians working for Kaiser Permanente in California and Hawaii voted to strike when the provider rejected their union’s proposals to increase staffing. Some locations are still without a contract. Kaiser, however, has spotlighted La Clínica as a diversity and inclusion success story to be replicated.
“My community has been decimated,” Dominguez says through tears. “My colleagues are devastated. They can’t work for a company who doesn’t value them and who wants to harm their community by depriving them of what they need.”
Giving communities what they need requires a rethinking. Youins, for his part, has seen that equitable, culturally competent mental health care is possible and can be life-changing. But even though individual organizations and providers have taken inspiring and meaningful steps toward mental health parity, they alone cannot fix the crisis of inequity. The fundamental problem is bigger than them, bigger than the health-care system in which they work. It is ingrained in the foundations of American society. This is why Hansen and others argue that improving access to traditional care is not enough.
Equitable mental health care requires equity across all aspects of life. The foundational drivers of health—access to nutritious food, a clean environment, job security, freedom from racism and police brutality—are bound to structural inequities, namely, racism. “As a mental health provider, I see it in my patients all the time,” says Michael Mensah, a psychiatrist at the Yale School of Medicine. “They have things I can’t medicate away. They have things I can’t therapy away.”
Yet people have a remarkable ability to persevere, given the opportunity. Youins sees this resiliency when he meets with his Imani Breakthrough group, which gathers at one of the oldest Black churches in New Haven. There, he says, “people are finding miracles within themselves.”
“The traditional way has its place,” Youins says. “But I think we need to look at some things differently.”
It was a small trial, just 18 rectal cancer patients, every one of whom took the same drug.
But the results were astonishing. The cancer vanished in every single patient, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans.
Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, an author of a paper published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the drug company GlaxoSmithKline, said he knew of no other study in which a treatment completely obliterated a cancer in every patient.
“I believe this is the first time this has happened in the history of cancer,” Dr. Diaz said.
Dr. Alan P. Venook, a colorectal cancer specialist at the University of California, San Francisco, who was not involved with the study, said he also thought this was a first.
A complete remission in every single patient is “unheard-of,” he said.
These rectal cancer patients had faced grueling treatments — chemotherapy, radiation and, most likely, life-altering surgery that could result in bowel, urinary and sexual dysfunction. Some would need colostomy bags.
They entered the study thinking that, when it was over, they would have to undergo those procedures because no one really expected their tumors to disappear.
But they got a surprise: No further treatment was necessary.
“There were a lot of happy tears,” said Dr. Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center and a co-author of the paper, which was presented Sunday at the annual meeting of the American Society of Clinical Oncology.
Another surprise, Dr. Venook added, was that none of the patients had clinically significant complications.
On average, one in five patients have some sort of adverse reaction to drugs like the one the patients took, dostarlimab, known as checkpoint inhibitors. The medication was given every three weeks for six months and cost about $11,000 per dose. It unmasks cancer cells, allowing the immune system to identify and destroy them.
While most adverse reactions are easily managed, as many as 3 percent to 5 percent of patients who take checkpoint inhibitors have more severe complications that, in some cases, result in muscle weakness and difficulty swallowing and chewing.
The absence of significant side effects, Dr. Venook said, means, “either they did not treat enough patients or, somehow, these cancers are just plain different.”
In an editorial accompanying the paper, Dr. Hanna K. Sanoff of the University of North Carolina’s Lineberger Comprehensive Cancer Center, who was not involved in the study, called it “small but compelling.” She added, though, that it is not clear if the patients are cured.
“Very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” Dr. Sanoff said in the editorial.
Dr. Kimmie Ng, a colorectal cancer expert at Harvard Medical School, said that while the results were “remarkable” and “unprecedented,” they would need to be replicated.
The inspiration for the rectal cancer study came from a clinical trial Dr. Diaz led in 2017 that Merck, the drugmaker, funded. It involved 86 people with metastatic cancer that originated in various parts of their bodies. But the cancers all shared a gene mutation that prevented cells from repairing damage to DNA. These mutations occur in 4 percent of all cancer patients.
Patients in that trial took a Merck checkpoint inhibitor, pembrolizumab, for up to two years. Tumors shrank or stabilized in about one-third to one-half of the patients, and they lived longer. Tumors vanished in 10 percent of the trial’s participants.
That led Dr. Cercek and Dr. Diaz to ask: What would happen if the drug were used much earlier in the course of disease, before the cancer had a chance to spread?
They settled on a study of patients with locally advanced rectal cancer — tumors that had spread in the rectum and sometimes to the lymph nodes but not to other organs. Dr. Cercek had noticed that chemotherapy was not helping a portion of patients who had the same mutations that affected the patients in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew.
Perhaps, Dr. Cercek and Dr. Diaz reasoned, immunotherapy with a checkpoint inhibitor would allow such patients to avoid chemotherapy, radiation and surgery.
New Developments in Cancer Research
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Progress in the field. In recent years, advancements in research have changed the way cancer is treated. Here are some recent updates:
Pancreatic cancer. Researchers managed to tame advanced pancreatic cancer in a woman by genetically reprogramming her T cells, a type of white blood cell of the immune system, so they can recognize and kill cancer cells. Another patient who received the same treatment did not survive.
Chemotherapy. A quiet revolution is underway in the field of cancer treatment: A growing number of patients, especially those with breast and lung cancers, are being spared the dreaded treatment in favor of other options.
Leukemia. After receiving a new treatment, called CAR T cell therapy, more than a decade ago, two patients with chronic lymphocytic leukemia saw the blood cancer vanish. Their cases offer hope for those with the disease, and create some new mysteries.
Esophageal cancer. Nivolumab, a drug that unleashes the immune system, was found to extend survival times in patients with the disease who took part in a large clinical trial. Esophageal cancer is the seventh most common cancer in the world.
Dr. Diaz began asking companies that made checkpoint inhibitors if they would sponsor a small trial. They turned him down, saying the trial was too risky. He and Dr. Cercek wanted to give the drug to patients who could be cured with standard treatments. What the researchers were proposing might end up allowing the cancers to grow beyond the point where they could be cured.
“It is very hard to alter the standard of care,” Dr. Diaz said. “The whole standard-of-care machinery wants to do the surgery.”
Finally, a small biotechnology firm, Tesaro, agreed to sponsor the study. Tesaro was bought by GlaxoSmithKline, and Dr. Diaz said he had to remind the larger company that they were doing the study — company executives had all but forgotten about the small trial.
Their first patient was Sascha Roth, then 38. She first noticed some rectal bleeding in 2018 but otherwise felt fine — she is a runner and helps manage a family furniture store in Bethesda, Md.
During a sigmoidoscopy, she recalled, her gastroenterologist said, “Oh no. I was notexpecting this!”
The next day, the doctor called Ms. Roth. He had had the tumor biopsied. “It’s definitely cancer,” he told her.
“I completely melted down,” she said.
Soon, she was scheduled to start chemotherapy at Georgetown University, but a friend had insisted she first see Dr. Philip Paty at Memorial Sloan Kettering. Dr. Paty told her he was almost certain her cancer included the mutation that made it unlikely to respond well to chemotherapy. It turned out, though, that Ms. Roth was eligible to enter the clinical trial. If she had started chemotherapy, she would not have been.
Not expecting a complete response to dostarlimab, Ms. Roth had planned to move to New York for radiation, chemotherapy and, possibly surgery after the trial ended. To preserve her fertility after the expected radiation treatment, she had her ovaries removed and put back under her ribs.
After the trial, Dr. Cercek gave her the news.
“We looked at your scans,” she said. “There is absolutely no cancer.” She did not need any further treatment.
But two years later, she still does not have a trace of cancer.
Gina Kolata writes about science and medicine. She has twice been a Pulitzer Prize finalist and is the author of six books, including “Mercies in Disguise: A Story of Hope, a Family’s Genetic Destiny, and The Science That Saved Them.” @ginakolata • Facebook
Memories are like scenes in a movie, and the brain is an excellent video editor.
Take a normal day as an example. A morning routine—shower, coffee, checking emails—is seamlessly cut into one continuous scene. Other goings-on throughout the day become separate cuts, so when recalling one memory—a fabulous bagel sandwich deli, for example—the memory pops into the mind on its own. Yet ultimately we still retain a continuous narrative of our lives that shapes who we are, without memories blending into each other in an incomprehensible plot.
How does the brain do that?
A new study in Nature points to a surprising clue—a protein called CCR5. The name may sound familiar. It’s well known as an entryway for HIV infection. It’s also the gene that skyrocketed to fame in 2018, when a rogue scientist used CRISPR-Cas9 to engineer the world’s first gene-edited babies, triggering a global backlash and landing him in prison.
Part of the worry for the babies is that CCR5 is a multitasker. In the brain, for example, it dwells in cells at high levels in the hippocampus, a region critical for memory. CCR5 has previously been linked to memory functions, prompting questions on how the edits could alter the babies’ cognition down the line.
The new study offers additional clues. In mice, CCR5 acts as the scissor tool in video editing. As the brain continuously processes new experiences into memories, high levels of CCR5 essentially snip the timeline into distinct episodes. While normally helpful, CCR5 levels rise during aging and often become overzealous. The result is memory loss—a mind that struggles to link memories into comprehensive events.
“Our memories are a huge part of who we are,” said study lead author Dr. Alcino Silva at the David Geffen School of Medicine at UCLA. “The ability to link related experiences teaches us how to stay safe and operate successfully in the world.”
The good news? Using an FDA-approved drug for HIV treatment, the team restored an aging mind’s ability to link memories in mice, “a result that could have substantial clinical implications,” the team said.
Let’s Talk Memory
Memories may seem like amorphous wisps inside a mind, but they have strong neurobiological underpinnings.
When we encounter new experiences, a select group of neurons inside a part of the hippocampus encodes these data. How these neurons are selected is still relatively mysterious, but scientists have engineered ways to “prime” certain neurons to participate in the memory so that they’re more active and likely to participate.
Once a memory is stored, this network of neurons is called an engram. The process is very loosely similar to a computer allocating memory storage to save a new document. Activating any component of the engram triggers the whole network to activate, which retrieves the memory.
This process relies on a dance of a myriad of proteins. Neurons are like hotels with multiple protein locks—receptors—and keys, called ligands. The locks are generally dotted on the surface of the cell. Each requires the right key to unlock it. Unlocking triggers a cascade of molecule signaling inside cells, which eventually changes how a neuron behaves; it might get more excitable, or more inhibited and less inclined to network with others. Less networking means less memory encoding, and potentially less memory linking.
“How does the brain know that two events are occurring closely in time? Addressing this question requires an understanding of how time is encoded in memory—a major unknown in memory research,” said Andrea Teceros and Dr. Priya Rajasethupathy at the Rockefeller University, who were not involved in the study.
Molecular Memento
In the new study, the team honed in on CCR5 as a key protein to delink a memory stream. Although mostly known as part of the immune system, CCR5 is a receptor highly expressed in the hippocampus, and previous studies suggested a potential role in memory.
The team began with a popular setup for memory tests for mice. They first placed the mice into one cage to explore, and five hours later, placed them into a different cage with wildly different decorations. Here the mice received a quick and mild electrical zap, enough to startle them and make them freeze in fear. This encoded two different memories. Two days later, when placed back into the first benign cage, the mice also froze—showing that they’ve linked the first cage and the second, where they actually received the shock, into one memory.
The time gap was key. When the team extended the five-hour gap between the two cages to 24 hours, the mice could no longer link the memories.
The switch turned out to be CCR5. The protein levels briefly shot up 12 hours after the initial encoding, and tanked soon after—a trajectory that parallels the time course for memory linking. Genetically deleting or inhibiting CCR5 prolonged the memory linking window so that the mice could still hook up memories of the two cages up to seven days apart. In contrast, increasing CCR5 further dampened the mice’s ability to link those memories.
Digging deeper, CCR5 seems to directly tinker with neural activity in the hippocampus—the memory ledger—to dampen its activity. Two memories close in time often share overlapping engrams. Here, mice without CCR5 had greater overlaps between memories of the two cages and higher memory linking compared to normal counterparts.
Aging Memory Treatment?
Like most immune molecules, CCR5 levels rise with age, suggesting they may increasingly hack apart memories. This led the team to wonder: can we inhibit the protein to boost memory function with age?
They tested the theory in middle-aged mice with an FDA-approved drug for HIV, maraviroc, that inhibits the protein’s functions. A single infusion directly into the “memory center” hippocampus improved the aging animal’s ability to link memories, spread five hours apart, in a subsequent test. Similarly, middle-aged mice genetically lacking CCR5 also linked up memories better than their normal peers.
“When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA…the older animals were able to link memories again,” said Silva.
To Terceros and Rajasthupathy, the results could help with memory loss. “Because memory deficits in aging and in Alzheimer’s disease might be dominated by deficits in retrieval (and thus memory linking) rather than memory storage, which involves separate brain circuits, these results could have clinical implications.”
The study is one of the first to interrogate the brain’s clock for memory linking and segregation. It opens up a world of new questions. How does memory linking affect learning? Can it help “time-stamp” memories during storage in the mind? As an immune molecule, how does CCR5 further influence memory and other cognitive functions? And what, if anything, happens when human embryos are shoddily deprived of the molecule, as in the case of the CRISPR babies?
For now, the team is mostly eyeing CCR5’s therapeutic potential. “Our next step will be to organize a clinical trial to test maraviroc’s influence on early memory loss with the goal of early intervention,” said Silva. “Once we fully understand how memory declines, we’ll possess the potential to slow down the process.”
Shelly Xuelai Fan is a neuroscientist-turned-science writer. She completed her PhD in neuroscience at the University of British Columbia, where she developed novel treatments for neurodegeneration. While studying biological brains, she became fascinated with AI and all things biotech. Following graduation, she moved to UCSF to study blood-based factors that rejuvenate aged brains. She is the …
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COVID-19 and PTSD: Assessing the Pandemic’s Toll on Mental Health
January 02, 2022
Illness, grief, job loss, social isolation, uncertainty, and other pandemic-driven stressors have contributed to an increase in psychological distress on an unusually wide scale. As researchers and clinicians continue to grapple with the psychological fallout from COVID-19, a growing body of literature has examined the prevalence of post-traumatic stress disorder (PTSD) in the general public.
Women’s Health Research at Yale, in partnership with colleagues at the University of Bordeaux in France and the U.S. Department of Veterans Affairs National Center for PTSD, published a paper in the journal Chronic Stress identifying 36 studies assessing PTSD symptoms in the general population, and the occurrence of these symptoms ranged from 5 percent to 55 percent of those being studied, averaging 26 percent across the studies.
How can these estimates vary so greatly, and can such wide swaths of the public truly be suffering from pandemic-related PTSD? Before the pandemic, about 3.5 percent of American adults every year were diagnosed with PTSD, with women twice as likely as men to have the disorder.
Can the public truly be suffering from PTSD?
The American Psychiatric Association defines PTSD as a disorder in which someone experiences “intense, disturbing thoughts and feelings” for long periods following a traumatic event. Such a diagnosis requires, in part, that the event involve “actual or threatened death, serious injury, or sexual violence” either directly; as a witness; or learning of a loved one’s serious injury, encounter with sexual violence, or violent or accident death.
Dr. Mathilde Husky, professor of clinical psychology at the University of Bordeaux and lead author of the paper, notes that a life-threatening medical condition does not qualify unless it involves sudden or catastrophic events, such as waking up during surgery or anaphylactic shock. Husky and her co-authors question whether the pandemic “as a disruptive global experience can be construed as direct exposure to a traumatic event in the general population.”
Dr. Mathilde Husky
Dr. Mathilde Husky, previously a postdoctoral student with Dr. Mazure and now a professor at the University of Bordeaux, is lead author of a study on classifying the pandemic’s effect on mental health.
“As clinicians, when we ask about symptoms of PTSD, it’s always in reference to a specific traumatic event, with a significant level of shock,” Husky said. “In the context of a pandemic that is nearing two years in length, if I ask someone if they are experiencing flashbacks, the question becomes: flashbacks of what? Are they avoiding cues in their environment or situations that would expose them to things that would remind them of the event? Some people report a singular traumatic event in the context of the pandemic, but many do not.”
These findings have led the authors to question whether the pandemic can be considered as a single entity when it can affect people in so many different ways over such a long period of time, depending on their jobs, exposure to the disease, preexisting stressors and psychopathology, and many other factors. And, as important, whether other existing classifications adequately address the health needs of individuals who experience stress not as a single event but as an enduring experience with varying levels of severity or shock.
The authors, including Drs. Robert Pietrzak of Yale and the National Center for PTSD and Brian Marx at the National Center for PTSD, suggest that the next research step should be to ensure that PTSD criteria are met when evaluating PTSD or consider another, alternative way of classifying perceived stress that is related to a long, ongoing adverse experience. In addition, the authors suggest researchers should gather data on preexisting mental health disorders and prior exposure to traumatic events to better determine the source of more recent symptoms.
“We must also continue to focus on how preexisting and concurrent stressors may disproportionately affect women more than men,” said Dr. Carolyn M. Mazure, senior author on the paper and director of WHRY. “There is a growing body of evidence showing that lockdowns, school closures, and working from home to reduce the spread of COVID-19, for example, have had a greater effect on women. Is this because women have greater ongoing stressors?”
Norma Weinberg Spungen and Joan Lebson Bildner Professor in Women’s Health Research and Professor of Psychiatry and of Psychology; Director, Women’s Health Research at Yale
An estimated 280 million people suffer from depression globally, making it one of the most common mental disorders and the leading cause of disability worldwide, according to the World Health Organization. Its prevalence and the vast unmet need for care led Leaps by Bayer, the impact investment arm of Bayer AG, to make its first investment in mental health with Woebot Health. Dr. Jürgen Eckhardt, Head of Leaps by Bayer, explains why.
You’ve made a $9.5 million strategic investment in Woebot Health, your first in mental health. What prompted it?
Our investment strategy centers around solving 10 of the greatest challenges we see facing humanity today. We call those challenges Leaps, and we revisit and reevaluate them every other year or so. We recognized the increased prevalence of and unmet need in mental health, with depression and anxiety highest on the list. As such we created Leap Five – Protect the Brain and Mind – to address both central nervous system disorders and mental health issues.
Why Woebot Health?
First, it’s a data-driven company that combines psychology and technology. Woebot Health has already produced a lot of rigorous clinical evidence supporting its approach, including numerous randomized control trials and observational studies. These studies are at the core of the company’s platform and products, which are based on sound and validated behavioral therapies: Cognitive Behavioral Therapy (CBT), Interpersonal Psychotherapy (IPT) and Dialectical Behavioral Therapy (DBT).
What else did you consider?
We also looked at the model they’re working to achieve. With mental health, you never know at what time of day or night someone may need support. Woebot Health is providing an AI-powered, chat-based tool that can be a 24/7 digital therapist. But Woebot is so much more than an app; it listens, learns and delivers personalized advice and solutions in an approachable, conversational manner. The innovation – and empathy – in that approach certainly differentiates it from all the apps out there. But also, they’re not trying to bypass the healthcare system or replace healthcare providers. They’re actually making it easier for providers to deliver care either through prescription digital therapeutics or non-prescription therapeutics. The end result is they’re not just trying to take something directly to consumers. Rather, they’re showing data to healthcare systems and working with them to show how this approach can be value saving or value driving.
Can you talk a bit more about the value you see Woebot Health providing to healthcare systems?
When you look at value-based healthcare, you look at emergency visits, the number of people who aren’t able to see a therapist, and what that ends up costing. Woebot Health can address not only the wide discrepancy between the number of providers and patients that need help, but also hopefully reduce emergency room visits that can result from inadequate care. This is a company that wants to integrate with the healthcare system to make lives easier not just for the patients, but also the providers, and ultimately provide savings while delivering better, more effective care.
What do you hope comes out of this investment?
I’d like people to have 24/7 access to digital behavioral health solutions to help with the unmet need. And to see Woebot Health develop both prescription and non-prescription therapeutics and bring these helpful mental health solutions to people around the world.
Can COVID make your brain shrink? A recent Oxford University study revealed changes in several parts of the brain after people contracted the virus, including those who experienced mild symptoms. Source: Al Jazeera
A recent Oxford University study revealed changes in several parts of the brain after people contracted the virus, including those who experienced mild symptoms.
We have known for some time now that COVID-19 can affect the nervous system.
Some people who contracted the SARS-CoV-2 virus have suffered from a number of neurological complications including confusion, strokes, impaired concentration, headaches, sensory disturbances, depression, and even psychosis, months after the initial infection.
Now, researchers at the University of Oxford have conducted the first major peer-reviewed study comparing the brain scans of 785 people, aged 51 to 81 of whom 401 had contracted COVID and 384 had not. There were, on average, 141 days between testing positive for COVID and the second brain scan.
The study revealed that, when compared to the scans of a control group, those who tested positive for COVID had greater overall brain shrinkage and more grey matter shrinkage and tissue damage in regions linked to smell and mental capacities months after the initial infection.
Although the research does shed some light on the ongoing symptoms of long COVID, I would caution against generalising the findings to the population at large before more research is conducted.
Researchers said even though the effects were more pronounced in older people who had been hospitalised for their symptoms, even those with mild symptoms had some changes.
“Despite the infection being mild for 96 percent of our participants, we saw a greater loss of grey matter volume, and greater tissue damage in the infected participants, on average 4.5 months after infection,” said Professor Gwenaëlle Douaud, lead author on the study. “They also showed greater decline in their mental abilities to perform complex tasks, and this mental worsening was partly related to these brain abnormalities.”
The study was conducted when the Alpha variant was dominant in Britain and is unlikely to include anyone infected with the Delta variant. The researchers also did not say if vaccination against COVID had any impact on the condition.
The scans they did reveal changes in several parts of the brain after people contracted COVID, including:
Greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus. The orbitofrontal cortex is the part of the brain that controls reward, emotion and fluctuations in mood and feelings of sadness. It is also involved in cognitive function and decision-making. The parahippocampal gyrus plays a role in the control of our emotions as well as an important role in memory retrieval and spatial awareness and processing. We have seen symptoms of depression, anxiety and “brain fog” where people are prone to memory issues after a COVID infection.
Greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex. This is the part of the brain for processing and perception of smell; it also helps link smells to certain memories and survival responses. Loss of sense of smell has been a hallmark symptom of COVID and this may explain why that is.
Greater reduction in global brain size, essentially meaning the participants’ brains were smaller after testing positive for COVID than when scanned before the infection.
It is not uncommon for our brains to shrink as we get older, the natural ageing process results in the loss of grey matter every year, on average between 0.2 percent and 0.3 percent, according to researchers.Sign up for Al JazeeraCoronavirus Newsletter
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But the study found that, compared with uninfected participants, those who contracted COVID – even those who had mild cases – lost between 0.2 percent and 2 percent between scans.
The study also found that participants who had suffered from COVID exhibited a greater decline in efficiency and attention when performing a complex cognitive task.
The Oxford study is the first study to make such a direct link between COVID infections and changes in the brain. It goes some way to providing us with the beginnings of an explanation about the myriad neurological symptoms people with long-COVID complain about, although researchers stress that more studies are needed.
We do not know whether the changes in the brain demonstrated in this study are long-term or permanent, or whether they would be the same for younger people, who generally (but not always) get milder COVID symptoms.
Since the study was conducted during the reign of the Alpha variant, more work needs to be done on those who contracted the Delta and Omicron variants to see if similar changes are found.
The timing of the study also means that the participants were unlikely to have been vaccinated. Now, with so many people vaccinated, it would be useful to know if the vaccines offer a layer of protection.
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