Tuesday, June 8, 2021

Study shows adaptive brain response to stress, and its absence in people with depression

"Learning more about how acute stress and chronic stress affect the brain may help in the development of treatment targets for depression," says Jessica Cooper, first author of the study and a post-doctoral fellow in Emory's Department of Psychology.

By Carol Clark

A new study identifies a novel biomarker indicating resilience to chronic stress. This biomarker is largely absent in people suffering from major depressive disorder, and this absence is further associated with pessimism in daily life, the study finds. 

Nature Communications published the research by scientists at Emory University. 

The researchers used brain imaging to identify differences in the neurotransmitter glutamate within the medial prefrontal cortex before and after study participants underwent stressful tasks. They then followed the participants for four weeks, using a survey protocol to regularly assess how participants rated their expected and experienced outcomes for daily activities. 

“To our knowledge, this is the first work to show that glutamate in the human medial prefrontal cortex shows an adaptive habituation to a new stressful experience if someone has recently experienced a lot of stress,” says Michael Treadway, senior author of the study and professor in Emory’s Department of Psychology and Department of Psychiatry and Behavioral Science. “Importantly, this habituation is significantly altered in patients with depression. We believe this may be one of the first biological signals of its kind to be identified in relation to stress and people who are clinically depressed.” 

“Learning more about how acute stress and chronic stress affect the brain may help in the identification of treatment targets for depression,” adds Jessica Cooper, first author of the study and a post-doctoral fellow in Treadway’s Translational Research in Affective Disorders Laboratory

The lab focuses on understanding the molecular and circuit-level mechanisms of psychiatric symptoms related to mood disorders, anxiety and decision-making. 

It’s long been known that stress is a major risk factor for depression, one of the most common and debilitating of mental illnesses. “In many ways, depression is a stress-linked disorder,” Treadway says. “It’s estimated that 80 percent of first-time depressive episodes are preceded by significant, chronic life stress.” 

Around 16 to 20 percent of the U.S. population will meet the criteria for a major depressive disorder during their lifetimes. Experts are predicting rates of depression to climb even further in the wake of the ongoing COVID-19 pandemic. During the pandemic, about four in 10 adults in the United States have reported symptoms of anxiety or depressive disorder, up from one in 10 who reported them in 2019, according to the Kaiser Family Foundation. 

“The pandemic has created more isolation for many people, while also increasing the amount of severe stressors and existential threats they experience,” Treadway says. “That combination puts a lot of people at high risk for becoming depressed.” 

Although the link between stress and depression is clearly established, the mechanisms underlying this relationship are not. Experiments with rodents have shown an association between the response of glutamate — the major excitatory neurotransmitter in the mammalian brain — and stress. The role of glutamate in humans with depression, however, has been less clear. 

The 88 participants in the current study included people without a mental health disorder and unmedicated patients diagnosed with a major depressive disorder. Participants were surveyed about perceived recent stress in their lives before they underwent experiments using a brain scanning technique known as magnetic resonance spectroscopy. 

While in the scanner, participants were required to alternate between performing two tasks that served as acute stressors: Putting their hand up to the wrist in ice water and counting down from the number 2,043 by steps of 17 while someone evaluated their accuracy. 

Brain scans before and after the acute stressor measured glutamate in the medial prefrontal cortex, an area of the brain involved with thinking about one’s state and forming expectations. Previous research has also found that this brain area is involved in regulating adaptive responses to stress. 

Participants submitted saliva samples while in the scanner, allowing the researchers to confirm that the tasks elicited a stress response by measuring the amount of the stress hormone cortisol in the sample. 

In healthy individuals, the brain scans revealed that glutamate change in response to stress in the medial prefrontal cortex was predicted by individual levels of recent perceived stress. Healthy participants with lower levels of stress showed increased glutamate in response to acute stress, while healthy participants with higher levels of stress showed a reduced glutamate response to acute stress. This adaptive response was comparatively absent in the patients diagnosed with depression. 

“The decrease in the glutamate response over time appears to be a signal, or a marker, of a healthy adaptation to stress,” Treadway says. “And if the levels remain high that appears to be a signal for maladaptive responses to stress.” 

The initial result was strong for the adaptation in healthy participants, but was in a modest sample size, so the researchers decided to see if they could replicate it. “Not only did we get a replication, it was an unusually strong replication,” Treadway says. 

The experiment also included a group of healthy controls who underwent scanning before and after performing tasks. Rather than stressful tasks, however, the controls were asked to place a hand into warm water or to simply count out loud consecutively. Their glutamate levels were not associated with perceived stress and they did not show a salivary cortisol response. 

To expand their findings, the researchers followed participants for four weeks after scanning. Every other day, the participants reported on their expected and experienced outcomes for activities in their daily lives. The results showed that glutamate changes that were higher than expected based on an individual’s level of perceived stress predicted an increased pessimistic outlook — a hallmark for depression. 

“We were able to show how a neural response to stress is meaningfully related to what people experience in their daily lives,” Cooper says. “We now have a large, rich data set that gives us a tangible lead to build upon as we further investigate how stress contributes to depression.” 

Emory co-authors of the study include former and current graduate students from the Treadway lab Victoria Lawlor, Shabnam Hossein and Andrew Teer; as well as current and former research assistants Makiah Nuutinen, Brittany DeVries, Daniel Cole, Chelsea Leonard and Emma Hahn. Additional authors include researchers from UCLA, the University of Arkansas, Princeton and McLean Hospital/Harvard Medical School. 

The work was supported by the National Institutes of Mental Health.

Related:

How the brain decides to make an effort

How chronic inflammation may drive down dopamine and motivation

Study reveals how the brain decides to make an effort


Wednesday, June 2, 2021

Flow of slushy sea ice predicts glacier calving

A view of Illusiat Glacier shows the ice melange (in the foreground) and the sheered off edge of the glacier where a massive ice sheet just broke away. (Jason Amundson)

Ice mélange, the mass of floating sea ice that buttresses many tidewater glaciers, plays a major role in the timing of calving icebergs, finds a new study published in Nature Geoscience

Scientists measured how just a tiny shift in the flow of a mélange, from smooth to slightly more chaotic, can predict up to one hour in advance that a massive hunk of ice will break off from a glacier, then crash into the ocean to form a new iceberg. 

“As a gateway to the ocean, ice mélange is critical to predictions of sea-level rise,” says Justin Burton, associate professor of physics at Emory University and co-author of the paper. “We’ve provided what may be the best, most high-resolution data ever on the dynamics of a mélange leading up to a major calving event. That helps us understand the forces determining how much ice melts into the ocean, and how fast it happens.” 

Ryan Cassotto, a glaciologist from the University of Colorado, Boulder, is lead author of the paper. Co-authors include Jason Amundson from the University of Alaska Southeast, Juneau; and Mark Fahnestock and Martin Truffer, both from the University of Alaska Fairbanks. 

The study’s data was drawn from Ilulissat, a World Heritage Site and the most productive tidewater glacier in Greenland, also known as Jakobshavn Glacier. Kilometer-sized icebergs that calve from Ilulissat often capsize, leading to glacial earthquakes and small tsunamis. 


Related:

Monday, May 24, 2021

Even children think money can be 'dirty' money, study finds

Experiments led by Emory psychologist Arber Tasimi found that children prefer non-stolen money offered by a "bad" person over stolen money offered by an "okay" person.

 By Carol Clark

When people deposit a $100 bill into their bank accounts, they don’t imagine that when they later withdraw $100 they will get the same bill. After all, the only thing that matters about money is its amount. A dollar is just like any other dollar — unless it comes with a tainted past. 
 
“People tend to imbue objects with essences,” says Arber Tasimi, assistant professor of psychology at Emory University. “We can be put off by objects that we know have a ‘bad’ essence because of an immoral history, like a sweater worn by Hitler. And money doesn’t appear to be an exception.” 

Tasimi’s latest work finds that children as young as five show an aversion to accepting “dirty” money. The journal Cognitive Science published the research, which Tasimi conducted with Susan Gelman, a psychologist at the University of Michigan. 

“This sensitivity to morality, even in the context of money, seems to emerge early,” Tasimi says. “The fact that children are making these distinctions adds to the evidence showing just how much we care about where things come from, particularly when they come from bad sources.” 

Tasimi heads the Morality and Development Lab at Emory. He’s particularly interested in moral conflict — how we wrestle with our desire for personal benefits versus our interest in the welfare of others. 

In previous research, Tasimi found that even babies prefer to take a single graham cracker offered to them by a “nice” puppet rather than two graham crackers offered by a “mean” puppet. But when the mean puppet offers them eight crackers, most babies “sell out.” 

For the current paper, Tasimi wanted to explore how a sense of morality tied to money develops in children. A series of experiments included participants in two age groups: 5-to-6-year-olds and 8-to-9-year-olds. The children were presented with various hypothetical scenarios: A person offering them a dollar. A person offering them a stolen dollar that they had found. A “bad” person who stole a dollar but was offering them a dollar they did not steal. And a “bad” person offering them a dollar that they had stolen. 

The results showed that the children significantly rejected “dirty” money. They much preferred non-stolen money offered by a “bad” person than stolen money offered by an “okay” person. 

“What we find over and over is that the morality of the money plays a critical role in whether people decide to take it,” Tasimi says. “Why would we imbue money with ‘badness’? I think that’s the million-dollar question.” 

In ongoing work, Tasimi is delving deeper into possible answers to the mystery. Does the source of the money matter because it could be tainted? Is it due to an aversion to profiting at the expense of others? Or is it because accepting the tainted money somehow endorses the immoral activity behind it? 

“I’m also intrigued by individual differences,” Tasimi adds. “Some people do treat a dollar like any other dollar, while others don’t. Why are some people bothered by ‘dirty’ money and others are not?”

Related:

Wednesday, April 28, 2021

Human antibiotic use threatens endangered wild chimpanzees

The number of chimpanzees in Gombe National Park, the site of Jane Goodall's groundbreaking field studies, are down to about 95. "By misusing antibiotics, people can actually harm not only themselves, but also the species they share an environment with," says Emory disease ecologist Thomas Gillespie.

By Carol Clark

It’s well established that infectious disease is the greatest threat to the endangered chimpanzees made famous by the field studies of Jane Goodall at Gombe National Park in Tanzania. Now, new research led by scientists at Emory University shows that nearly half of the fecal samples from wild chimpanzees contain bacteria that is resistant to a major class of antibiotics commonly used by people in the vicinity of the park. 

The journal Pathogens published the findings

“Our results suggest that antibiotic-resistant bacteria is actually spreading from people to non-human primates by making its way into the local watershed,” says Thomas Gillespie, senior author of the study and associate professor in Emory’s Department of Environmental Sciences and Rollins School of Public Health. “People are bathing and washing in the streams, contaminating the water with drug-resistant bacteria where wild chimpanzees and baboons drink.” 

The researchers tested for genes conferring resistance to sulfonamides — drugs often used by people in the region to treat diarrheal diseases — in fecal samples from humans, domestic animals, chimpanzees and baboons in and around Gombe National Park. They also tested stream water used by these groups. 

Sulfonamide resistance appeared in 74 percent of the human samples overall, 48 percent of chimpanzee samples, 34 percent of baboon samples, and 17 percent of the domestic animal samples. Sulfonamide also showed up in 19 percent of the samples taken from streams shared by people, domestic animals and wildlife. 

The researchers also tested all the groups in the study for genes conferring resistance to tetracycline — another class of antibiotics that is used much less frequently by people in the vicinity, likely due to its greater expense and the fact that it is less available in the area. As expected, very few of the fecal samples from any of the groups, and none of the water samples from the streams, showed evidence of tetracycline resistance. 

First author of the study is Michele Parsons, who did the work as an Emory doctoral student in Environmental Sciences. Parsons has since graduated and works at the Centers for Disease Control and Prevention (CDC). Co-authors include researchers from the Jane Goodall Institute, the CDC, the University of Minnesota and Franklin and Marshall College. 

Gillespie is a disease ecologist who helped pioneer the “One Health” approach to protect humans, ecosystems and biodiversity. His projects in Africa, including the collaboration with the Jane Goodall Institute in Tanzania, are focused on helping farmers subsisting amid fragmented forests co-exist with primates and other wildlife in ways that minimize the risk of pathogen exchange between species, known as “spillover.” The virus that causes AIDS, for example, spilled over from chimpanzees to people. 

“It’s important to consider both sides of the story — human health and well-being, as well as conservation of chimpanzees and other species,” Gillespie says. 

Human encroachment has taken a toll on the great apes, due to fragmented habitat and the exchange of pathogens. Today, the number of chimpanzees in Gombe National Park are down to about 95. 

Diarrheal diseases are common in the area and people often turn to cheap sulfonamide antibiotics that are available without a prescription at small stores that act as informal pharmacies, selling drugs, soap and other necessities. Wild chimpanzees also suffer from wasting diseases that can be related to bacterial and other enteric pathogens that affect their ability to maintain calorie intake and absorb nutrients. 

“The majority of people in our sampling harbored bacteria resistant to the sulfonamide medication they are taking,” Gillespie says. “In those cases, they’re spending their money on a drug that is not helping them get better. Overuse of such drugs creates the potential for more lethal, antibiotic-resistant ‘super bugs’ to emerge.” 

The research findings will now support the development of interventions. 

More guidance is needed locally regarding the proper use of antibiotics, Gillespie says. He adds that it is also important to improve hygiene for wash-related activities in area streams, as well as to improve disposal of human waste materials. 

“By misusing antibiotics, people can actually harm not only themselves, but also the species they share an environment with,” Gillespie says. “After drug-resistant bacteria jump into chimpanzees, it can further evolve with the chimpanzees and then spill back into humans. We need to be thinking about infectious diseases within evolutionary and ecological frameworks, something that’s not often done in medicine.” 

The study was funded by the Morris Animal Foundation, the Emory Global Health Institute, the Arcus Foundation, the Leo S. Guthman Foundation and the National Institutes of Health.

Related:

Zoo gorillas contract COVID, raising alarms for great apes in the wild

Valuing 'natural capital' vital to avoid next pandemic, experts warn

Disease poses risk to chimpanzee conservation, Gombe study finds

Wednesday, April 21, 2021

Georgia Aquarium otters join list of animals testing positive for SARS-CoV-2

Otters are Mustelids, a diverse group of carnivorous mammals that includes mink and ferret — two other species that have also become infected with SARS-CoV-2. (Getty Images)

By Carol Clark

The recent positive SARS-CoV-2 tests of Asian small-clawed otters at the Georgia Aquarium add to the mystery of why some animals may be more susceptible than others to the virus that causes COVID-19. 

“In one sense, it’s not surprising to see otters infected, because we’ve already seen infections in mink and ferrets, which are closely related species,” says Thomas Gillespie, associate professor in Emory University’s Department of Environmental Sciences and Rollins School of Public Health. 

Otters, mink and ferrets are all Mustelids, a diverse group of carnivorous mammals, notes Gillespie, a disease ecologist who studies how pathogens jump between wildlife, domestic animals and people.

Most of the research into what animal species may be susceptible to SARS-CoV-2 is based on the genetics of protein binding sites that the virus uses to gain a foothold in a host. People, great apes and some monkeys have the highest susceptibility, according to this research, Gillespie says. 

In January, some members of the gorilla troop at the San Diego Zoo tested positive for SARS-CoV-2, after they exhibited COVID-19 symptoms. 

“What’s surprising,” Gillespie says, “is that Mustelids are at the opposite end of the spectrum in terms of a binding propensity with SARS-CoV-2. In one of the more robust studies to date, they fell into the lower range of binding scores among 400 species of vertebrates. And yet, they keep popping up with infections. That’s where the mystery lies.” 

The Georgia Aquarium announced in an April 18 news release that the otters were tested after showing symptoms such as sneezing, runny noses, lethargy and coughing. The animals were removed from their exhibit for behind-the-scenes care and are expected to make a full recovery, the release stated. 

The virus that causes COVID-19 is zoonotic, meaning that it originated in animals — most likely horseshoe bats — and may have passed through another species before making its way to humans. 

“It’s critical right now for the world to focus on preventing human-to-human transmission of the virus,” Gillespie says. “But it’s also important to consider the longer-term, bigger picture of how pathogens can spill over from animals to people and then back to animals again.” 

Gillespie helped pioneer the One Health approach to protecting humans, ecosystems and biodiversity. The primary risks for future spillover of zoonotic diseases are deforestation of tropical environments and large-scale industrial farming of animals, he says. 

In late 2020, COVID-19 outbreaks were seen in mink around the world, including the United States, at farms that mass-produce the animals for the fur trade. The mink are kept in densely packed conditions that are ideal for spreading pathogens, Gillespie says. 

Denmark culled 17 million mink after the virus spread from the human caretakers to the animals, then mutated and spread back to some of the human caretakers. 

“The good news is that there are relatively few documented cases of animal transmission to humans, and these appear to be restricted to the most ideal conditions for transmission, such as the crowded conditions of industrial mink farming,” Gillespie says. 

Ferrets are a common laboratory model for the study of respiratory diseases, due to their unique respiratory biology. Experimental studies have shown that they can easily be infected with SARS-CoV-2. 

The black-footed ferret is among the most endangered mammals in North America. That prompted researchers at the U.S. National Wildlife Health Center last December to start testing a veterinary vaccine for COVID-19 on a captive population of the animals at the National Black-footed Ferret Conservation Center in Colorado. 

Almost all of the species that have tested positive for SARS-CoV-2, including cats, dogs, tigers, gorillas and a few other mammals, live in close proximity to people — either as pets, in zoos or in laboratories. One exception is a wild mink, found near a mink farm in Utah, that tested positive for SARS-CoV-2, according to the U.S. Department of Agriculture. 

“Testing of wildlife is rare,” Gillespie says. “And most testing of captive animals is done only if they show symptoms, suggesting there may be many more asymptomatic cases. There are a lot of important questions into how SARS-CoV-2 may affect animals that we have not yet started exploring.” 

The questions are important to protect both the health of animals and people, he adds. 

“Widespread infection within a population of a novel virus is the kind of event that could potentially push endangered and critically endangered species over the edge,” Gillespie says. “And any time a virus enters a new species with different selective pressures, that provides more opportunities for new mutants of the virus to evolve and potentially spill over into humans.”

Related:

San Diego Zoo gorillas contract COVID, raising alarms for great apes in the wild

Valuing 'natural capital' vital to avoid next pandemic

Bat ecology in the era of pandemics