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Chronic opioid treatment may raise risk of post-traumatic stress disorder, study finds

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Senior author Michael Fanselow said the research suggests that chronic opioid use increases susceptibility to developing anxiety disorders. Photo credit: Reed Hutchinson/UCLA

While opioids are often prescribed to treat people with trauma-related pain, a new UCLA-led study suggests doctors should use caution before prescribing the drug to those they believe may experience severe stress in the future, in order to reduce the risk the patient will develop PTSD.

In the study, researchers administered doses of the opioid morphine to a group of 22 mice for one week, then gave the mice relatively strong foot shocks. After the morphine wore off, the mice were given mild electric foot shocks. These mice showed a substantially longer “freezing response” than a second, control group of 24 mice that had not been given morphine. When mice recall a frightening memory, they freeze. Their heart rates and blood pressure go up, and the more frightening the memory, the more they freeze.

“While we are generally aware that drug use, such as that in the current opioid crisis, has many deleterious effects, our results suggest yet another effect — increased susceptibility to developing anxiety disorders,” said senior author Michael Fanselow, UCLA distinguished Staglin family professor of psychology and director of UCLA’s Staglin Family Music Festival Center for Brain and Behavioral Health. “As opioids are often prescribed to treat symptoms such as pain that may accompany trauma, caution may be needed because this may lead to a greater risk of developing PTSD, if exposed to further traumatic events, such as an accident, later on.”

“The foot shocks produced lasting fear and anxiety-like behaviors, such as freezing,” Fanselow said.

“Our data are the first to show a possible effect of opioids on future fear learning, suggesting that a person with a history of opioid use may become more susceptible to the negative effects of stress,” Fanselow said. “The ability of opioids to increase PTSD-like symptoms far outlasted the direct effects of the drug or withdrawal from the drug, suggesting the effect may continue even after opioid treatment has stopped.”

Fanselow’s view is if there is reason to believe a patient is likely to experience severe emotional stress after opioid treatment, then doctors should use caution about prescribing an opioid. If opioid use is medically called for, then the patient should be kept away from potentially stressful situations. So, for example, a soldier treated with opioids for pain should not be sent back into combat for a period of time, he said. The development of post-traumatic stress disorder requires some stressful experience after opioid use, he said.

The researchers also gave some of the mice morphine after the initial trauma had occurred but before exposing them to the second, mild stressor. They found that mice treated with morphine after the initial trauma did not show enhanced fear learning following exposure to the mild stressor. This finding suggests that chronic use of opioids before — but not after — a traumatic event occurs affects fear learning during subsequent stressful events.

The researchers concluded the mice given morphine were more susceptible to post-traumatic stress disorder than the control group of mice not given any opioids, and inferred that people with a history of using opioids are more susceptible to PTSD than the general population.

The study is published in Neuropsychopharmacology, an international scientific journal focusing on clinical and basic science research that advances understanding of the brain and behavior.

The research was funded by the National Institute on Drug Abuse and National Institute of Mental Health.

An opiate is a drug naturally derived from the opium poppy plant, such as heroin, morphine and codeine. Opioid is a broader term that includes opiates and any substance, natural or synthetic, that binds to the brain’s opioid receptors — which play a key role in controlling pain, rewards and addictive behaviors. Synthetic opioids include the prescription painkillers Vicodin and OxyContin, as well as fentanyl and methadone.

Substance abuse and PTSD often go hand-in-hand, Fanselow said, and people with PTSD often take drugs to self-medicate. Nearly 40% of people with PTSD also have a drug disorder.

Fanselow and colleagues reported last month that a traumatic brain injury causes changes in a brain region called the amygdala; and the brain processes fear differently after such an injury.

This article originally appeared in the UCLA Newsroom.

One of California’s iconic tree species offers lessons for conservation

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Picture of a valley oak tree.

The valley oak, the largest oak in California, grows to over 100 feet tall and provides habitat and food for a variety of animals. Photo credit: Victoria Sork/UCLA

 

With increasing regularity, Californians are witnessing firsthand the destructive power of wildfires. But not everyone sees what happens after the flames die down, when debris is cleared, homes and lives rebuilt — and trees replanted to help nature recover.

New research led by UCLA evolutionary biologist Victoria Sork examines whether the trees being replanted in the wake of California’s fires will be able to survive a climate that is continuing to warm.

The study, which is published in the Proceedings of the Natural Academy of Sciences, focuses on California’s iconic valley oak. The research is among the first to demonstrate the potential of using genomics to inform conservation strategies — essentially giving species an evolutionary boost. The study showed that planting trees that are genetically better suited to higher temperatures makes them more likely to survive and grow to maturity.

“When we think about managing ecosystems under rapidly changing climates, we have to realize trees need to be able to survive past 50 years,” Sork said.

The paper also discovered something surprising: The valley oak, an essential component of many ecosystems in California, is already poorly adapted to its environment — even considering climate conditions in 2019.

“They actually seem to grow better in cooler climates than they’re in right now,” said Luke Browne, a postdoctoral scholar at the UCLA La Kretz Center for California Conservation Science and the study’s lead author. “They might grow better if climates were more like they were 21,000 years ago, during the last ice age.”

During the peak of the last ice age, summer temperatures were about 4 to 5 degrees Celsius colder, and ice covered most of Canada and mountainous areas of the U.S.

In the fields of conservation and land management, it is a common assumption that plants and animals are adapted to their environments — that’s how evolution and natural selection are supposed to work. The new research casts doubt on that assumption.

The study is part of an ongoing project initiated by Sork and Jessica Wright, an expert in conservation genetics at the USDA Forest Service, more than 10 years ago.

Researchers gathered 11,000 seeds from 94 locations throughout the trees’ range, which stretches from the Santa Monica Mountains to the Cascade foothills in the northern part of the state. They grew them to saplings in a greenhouse and planted them in two large experimental gardens, in Chico and Placerville, California. They tracked how well trees from different locations grew, and sequenced the genomes of their mother trees to link genetic information and growth rates.

The researchers then identified which genetic variants would be more likely to thrive as climate change continues to warm California. They predicted that, under predicted future warmer temperatures, trees containing beneficial genetic variations would have 11% higher growth rates than the average for all of the trees in the experiment, and 25% higher growth rates than the trees without the beneficial variations.

Information like that could help the U.S. Forest Service, for example, in its efforts to restore forests with species that have the best chance for long-term survival.

“Studies like this one provide valuable insights that help land managers make informed decisions on reforestation projects,” Wright said. “When planting trees in a particular location, managers have to decide where to collect the acorns.”

By 2070, average temperatures in the state are projected to be up to 4.8 degrees warmer than they were during the mid- to late 20th century.

“That’s going to have consequences for how fast these trees grow,” Browne said. “We’re at a challenging time to figure out the best way to do conservation science. This paper shows one approach we could use that takes advantage of modern genomics.”

The study did not determine why valley oaks are not well adapted to their environment. It might be because the climate has already warmed up so much, the trees’ long lifespans — up to 500 years — or some other, unknown factor.

The valley oak is the largest oak in California; it grows to over 100 feet tall, and has dark green leaves and a deeply grooved trunk. It is considered a foundational species because it provides habitat and food for a variety of animals, including squirrels, birds, deer and insects. In parts of the state, it is one of the only species of tree that exists. Valley oaks provide benefits to humans, too: filtering water and providing shady places to escape the heat.

Although it focuses on the oak, the paper has broader implications for conservation science in a changing climate — especially for species that evolve and adapt slowly. That’s what Sork and Wright were thinking when they initiated the project.

At the time, they hoped to find conservation strategies that could eventually be implemented using genetic information alone — without extensive field experiments.

“Not everyone in the world is going to be able to collect 11,000 seeds and plant them in a common garden,” Sork said.

This article originally appeared in the UCLA Newsroom.

UCLA political scientists launch one of largest-ever public opinion surveys for run-up to 2020

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As the nation heads into another contentious presidential campaign, what will drive people’s choices? What sacrifices are Americans willing to make to see their preferred politicians take office and their policy preferences take hold?

UCLA political science professors Lynn Vavreck and Chris Tausanovitch plan to tackle those questions through the 2020 election with an ambitious data-gathering and analysis project called Nationscape. The effort is a partnership with the Washington, D.C.-based Democracy Fund, and the surveys are being fielded by Lucid, a New Orleans-based market research firm.

Every week until the end of 2020, Nationscape will survey 6,250 Americans, asking them to choose between two groups of policy positions and political attributes, among hundreds of other questions.

What makes Nationscape unique is the way it asks respondents to make choices. The survey includes 41 different policy statements and eight hypothetical attributes of potential candidates, all of which are randomized to appear in two sets of issues that voters must choose between. For example, respondents could be asked to choose one of the following sets of statements:

Each bundle of policies and outcomes could contain views that respondents disagree with, mixed with ideas they favor, but Vavreck said posing the questions that way will give researchers a better sense of what really makes the electorate tick.

“We designed the project to learn what people’s priorities are when they are forced to choose among states of the world they want to live in,” she said. “This will help us sort out what is really important to people who, in traditional surveys, tell us they ‘strongly agree’ with all sorts of issues. That response doesn’t really tell us how people will vote if a choice has to be made, and voting is all about making a choice.”

Researchers will share insights and analysis from the surveys regularly throughout election season on Nationscape’s website. By November 2020, the team will have completed a half million interviews — including at least 1,000 interviews in every congressional district.

“Our measurement approach, coupled with the massive scope of the project, will allow us to track both attitude change and shifts in the impact or importance of issues and candidate traits over time and space,” Vavreck said.

Data gathering began in late July. Among the initial findings: Even when Democrats and Republicans agree that children shouldn’t be separated from their parents at the southern border, that there should be a pathway to citizenship for people brought to the U.S. as children, or that the size of the military should be preserved, Democrats are more likely than Republicans to concede on the other issues to preserve their preferred stances on immigration issues, while Republicans are more likely to make tradeoffs to preserve the military.

The results also hint at how people’s priorities change — or don’t — in relation to current events. For example, Vavreck said, few people changed their opinions about the need for universal background checks for gun purchases after the mass shootings in El Paso, Texas, and Dayton, Ohio.

“But the importance of that issue changed quite a bit,” she said. “It became significantly more important to people in choosing policy packages after the shootings, even though only about 1.8 percent of them changed their positions on the issue.”

Vavreck is the co-author of critically acclaimed books about the two most recent presidential elections, “The Gamble: Choice and Chance in the 2012 Presidential Election” and “Identity Crisis: The 2016 Presidential Campaign and the Battle for the Meaning of America.” She is UCLA’s Marvin Hoffenberg Professor of American Politics and Public Policy.

Tausanovitch, an expert on political representation, is the co-principal investigator — along with Chris Warsaw of George Washington University — of the American Ideology Project, which characterizes the conservativism and liberalism of states and voting districts through a 275,000-person survey.

Tausanovitch combed through studies, programs and policies to develop the lists of scenarios that respondents are confronting in the Nationscape surveys. He’s interested in the tradeoffs people are willing to make based on their political leanings and where they come from.

“Data is already demonstrating to us the way people’s attitudes and priorities change in response to events taking place in the country and showing us how Democrats and Republicans prioritize things differently, even when they agree on policies,” Tausanovitch said. “This helps to explain how Americans agree on many things, but also illustrates that their priorities are different.”

The overarching goal of Nationscape is to engender more informed and productive political deliberations, said Joe Goldman, president of the Democracy Fund.

“Nationscape goes beyond horse race polls and battleground states and gets to the real issues that are driving voters and their decisions,” he said. “The unparalleled size and scope of this survey will help us understand how opinions differ across small geographic areas and groups of voters in a way that isn’t possible with traditional surveys, providing a deeper understanding of the electorate in this vital election.”

By the end of the election cycle, Nationscape will have reached people in every state and congressional district, America through Lucid’s platform.

“We were very eager to partner with the UCLA team and help apply their expertise on a scale that reflects the complexity of contemporary American politics,” said Patrick Comer, Lucid’s founder and CEO.

This article originally appeared in the UCLA Newsroom.

UCLA astronomer gets best look at first comet from outside our solar system

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The comet 2I/Borisov, as seen on Oct. 12 with NASA’s Hubble Space Telescope. Scientists believe the comet is from another solar system. Photo credit: NASA, ESA and David Jewitt/UCLA

David Jewitt, a UCLA professor of planetary science and astronomy, has captured the best and sharpest look at a comet from outside of our solar system that recently barged into our own. It is the first interstellar comet astronomers have observed.

Comet 2I/Borisov (the “I” stands for interstellar) is following a path around the sun at a blazing speed of approximately 110,000 miles per hour, or about as fast as Earth travels around the sun. Jewitt studied it on Oct. 12 using NASA’s Hubble Space Telescope, which captured images of the object when it was about 260 million miles away. He observed a central concentration of dust around the comet’s solid icy nucleus — the nucleus itself is too small to be seen by Hubble — with a 100,000-mile-long dust tail streaming behind.

Jewitt said it’s very different from another interstellar object, dubbed ‘Oumuamua, that a University of Hawaii astronomer observed in 2017 before it raced out of our solar system.

“‘Oumuamua looked like a bare rock, but Borisov is really active — more like a normal comet,” said Jewitt, who leads the Hubble team. “It’s a puzzle why these two are so different. There is so much dust on this thing we’ll have to work hard to dig out the nucleus.”

That work will involve sophisticated image processing to separate the light scattered from the nucleus from light scattered by dust.

► View a 2-second time lapse video of the comet

2I/Borisov and ‘Oumuamua are the first two objects that have traveled from outside of our solar system into ours that astronomers have observed, but that’s because scientists’ knowledge and equipment are much better now than they ever have been, and because they know how to find them. One study indicates there are thousands of such comets in our solar system at any given time, although most are too faint to be detected with current telescopes.

Until 2I/Borisov, every comet that astronomers have observed originated from one of two places. One is the Kuiper belt, a region at the periphery of our solar system, beyond Neptune, that Jewitt co-discovered in 1992. The other is the Oort Cloud, a very large spherical region approximately a light-year from the sun, which astronomers think contains hundreds of billions of comets.

2I/Borisov was initially detected on Aug. 30 by Gennady Borisov at the Crimean Astrophysical Observatory, when it was 300 million miles from the sun. Jewitt said its unusually fast speed — too fast for the sun’s gravity to keep it bound in an orbit — indicates that it came from another solar system and that it is on a long path en route back to its home solar system.

Because the comet was presumably forged in a distant solar system, the comet provides valuable clues about the chemical composition and structure of the system where it originated.

2I/Borisov will be visible in the southern sky for several months. It will make its closest approach to the sun on Dec. 7, when it will be twice as far from the sun as Earth is. By the middle of 2020, it will pass Jupiter on its way back into interstellar space, where it will drift for billions of years, Jewitt said.

Comets are icy bodies thought to be fragments left behind when planets form in the outer parts of planetary systems.

20 new moons for Saturn

In separate research that has not yet been published, Jewitt is part of a team that has identified 20 previously undiscovered moons of Saturn, for a new total of 82 moons. The revised figure gives Saturn more moons than Jupiter, which has 79.

The new objects are all small, typically a few miles in diameter, and were discovered using the Subaru telescope on Maunakea in Hawaii. They can be seen only using the world’s largest telescopes, Jewitt said.

The moons might have formed in the Kuiper belt, said Jewitt, a member of the National Academy of Sciences and a fellow of the American Association for the Advancement of Science and of the American Academy of Arts and Sciences.

The research team was headed by Scott Sheppard, a staff scientist at the Carnegie Institution for Science, and includes Jan Kleyna, a postdoctoral scholar at the University of Hawaii.

This article originally appeared in the UCLA Newsroom.

UCLA receives $20 million to establish UCLA Bedari Kindness Institute

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Jennifer and Matthew C. Harris ‘84.

The Bedari Foundation, established by philanthropists Jennifer and Matthew C. Harris, has given $20 million to the UCLA College to establish the UCLA Bedari Kindness Institute.

The institute, which is housed in the division of social sciences, will support world-class research on kindness, create opportunities to translate that research into real-world practices, and serve as a global platform to educate and communicate its findings. Among its principal goals are to empower citizens and inspire leaders to build more humane societies.

“Universities should always be places where we teach students to reach across lines of difference and treat one another with empathy and respect — even when we deeply disagree,” UCLA Chancellor Gene Block said. “The UCLA Bedari Kindness Institute will bring the best thinking to this vital issue and, I think, will allow us to have a real social impact on future generations.”

The institute, which will begin operating immediately, will take an interdisciplinary approach to understanding kindness — through evolutionary, biological, psychological, economic, cultural and sociological perspectives. It will focus on research about the actions, thoughts, feelings and social institutions associated with kindness and will bring together researchers from across numerous disciplines at UCLA and at external organizations.

The inaugural director of the institute is Daniel Fessler, a UCLA anthropology professor whose research interests include exploring how witnessing acts of remarkable kindness can cause an uplifting emotional experience that in turn motivates the observer to be kind. Studies by Fessler and his colleagues have shed light on why some people are open to that type of “contagious kindness” experience.

The Bedari Foundation is a private family foundation whose aim is to enable significant cultural shifts in the fields of health and wellness, community displacement and environmental conservation.

“Our vision is that we will all live in a world where humanity discovers and practices the kindness that exists in all of us,” said Matthew Harris, the foundation’s co-founder and a 1984 UCLA graduate. “Much research is needed to understand why kindness can be so scarce in the modern world. As we seek at Bedari to bridge the divide between science and spirituality, through the establishment of the UCLA Bedari Kindness Institute we hope to educate and empower more and more people in the practice of kindness.”

Already, a range of researchers at UCLA are studying the types of questions that will be the basis of the institute’s work. For example, UCLA anthropologists are examining how kindness spreads from person to person and group to group. UCLA sociologists are analyzing how people who regularly act unkind might be encouraged to engage in kind acts instead, and UCLA psychologists are researching how kindness can improve people’s moods and reduce symptoms of depression. Others are pursuing research on changes in neurobiology and behaviors resulting from mindfulness, and how those changes can influence kindness and people’s mental, physical and social well-being.

“In the midst of current world politics, violence and strife, the UCLA Bedari Kindness Institute seeks to be an antidote,” said Darnell Hunt, dean of the UCLA division of social sciences. “Rooted in serious academic work, the institute will partner and share its research on kindness broadly in accessible formats. The Bedari Foundation’s extraordinary gift is truly visionary and we are grateful for its support and leadership.”

The Kindness Institute will provide seed funding for research projects that examine the social and physical mechanics of kindness and how kindness might be harnessed to create more humane societies. It also will provide mindfulness awareness training to students, faculty and staff and in underserved Los Angeles communities, and host an annual conference at which presenters will examine new discoveries in kindness research, among other activities.

“The mission of the Kindness Institute perfectly aligns with that of the division of social sciences, where engaging the amazing diversity and social challenges shaping Los Angeles routinely inspires research that has the potential to change the world,” Hunt said.

The gift is part of the Centennial Campaign for UCLA, which is scheduled to conclude in December.

Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota

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Senior author Elaine Hsiao says researchers hope to build on their current study to learn whether microbial interactions with antidepressants have consequences for health and disease. Photo: Reed Hutchinson/UCLA

A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines.

Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.

The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.

“Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,” said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.

Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.

That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?

In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.

If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinis. They found the bacterium transported significantly less serotonin.

The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.

“Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,” Fung said. “Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.”

The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. “For the future,” Hsiao said, “we want to learn whether microbial interactions with antidepressants have consequences for health and disease.” Hsiao wrote a blog post for the journal about the new research.

Other study co-authors are Helen Vuong, Geoffrey Pronovost, Cristopher Luna, Anastasia Vavilina, Julianne McGinn and Tomiko Rendon, all of UCLA; and Antoniya Aleksandrova and Noah Riley, members of Forrest’s team.

The research was supported by funding from the National Institutes of Health’s Director’s Early Independence Award, Klingenstein-Simons Fellowship Award, and David & Lucile Packard Foundation’s Packard Fellowship for Science and Engineering.

This article originally appeared in the UCLA Newsroom.

Minds Matter: Raising the Curtain on Depression and Anxiety

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Photo of Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske.

Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske.

UCLA students, community members and supporters joined Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske for a standing-room only hybrid class and public lecture on Monday, August 19, for “Minds Matter: Raising the Curtain on Depression and Anxiety,” a free hour-long discussion on the causes of depression and anxiety, public stigma, and potential advances for the future. The series was the first in an ongoing exploration of brain health that will continue with additional events focusing on bullying, aging well, and other topics.

Love, an NBA Champion and five-time NBA All-Star for the Cleveland Cavaliers, has publicly discussed his struggle with panic attacks and anxiety and his decision to seek therapy, and has become a leading voice in mental health advocacy and founded the Kevin Love Fund in 2018 with the mission of inspiring people to live their healthiest lives while providing the tools to achieve physical and emotional well-being.

“Mental health isn’t just an athlete thing, it’s an issue that affects everyone in some way. The more we can normalize the conversation around mental health, the more we can do to help those that are struggling,” said Love. “My goal in sharing my personal experience is to connect with others who are going through something and keep this dialogue top of mind.”

Michelle G. Craske is a UCLA Professor of Psychology, Psychiatry and Biobehavioral Sciences, Director of the Anxiety and Depression Research Center, and Associate Director of the Staglin Family Music Center for Behavioral and Brain Health. Craske has published extensively in the area of fear, anxiety and depression.

“We need to work together to bring anxiety and depression out of the dark. People who suffer will only seek help when they can do so without fear of shame. Event series such as ‘Minds Matter’ aim to shed a light on these critical issues, and to help make a positive breakthrough,” said Craske.

Craske also is Director of the Innovative Treatment Network within the UCLA Depression Grand Challenge, a campus-wide effort to cut the global burden of depression in half. The innovative treatment component, which Craske leads, seeks to develop novel and more effective treatments for depression and anxiety and increase the scalability and accessibility of existing evidence-based treatments.

The “Minds Matter” series leverages the strengths of UCLA College’s Psychology faculty as well as high-profile guests who provide specialized insight about the discussion topic. Upcoming sessions will include discussions on addiction, adolescent brain development and behavior, bullying, healthy aging, and thriving under stress. The “Minds Matter” series is made possible through the longstanding UCLA College and Geffen Playhouse partnership and the generous support of donors.

Check back for information on future “Minds Matter” events at  https://www.college.ucla.edu/seniorsurvey/minds-matter/.

Biochemists discover new insights into what may go awry in brains of people with Alzheimer’s

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Photo of two researchers in lab.

Research by UCLA professor Steven Clarke and former graduate student Rebeccah Warmack, as well as UCLA colleagues, reveals new information about the brain’s biochemistry.

More than three decades of research on Alzheimer’s disease have not produced any major treatment advances for those with the disorder, according to a UCLA expert who has studied the biochemistry of the brain and Alzheimer’s for nearly 30 years. “Nothing has worked,” said Steven Clarke, a distinguished professor of chemistry and biochemistry. “We’re ready for new ideas.” Now, Clarke and UCLA colleagues have reported new insights that may lead to progress in fighting the devastating disease.

Scientists have known for years that amyloid fibrils — harmful, elongated, water-tight rope-like structures — form in the brains of people with Alzheimer’s, and likely hold important clues to the disease. UCLA Professor David Eisenberg and an international team of chemists and molecular biologists reported in the journal Nature in 2005 that amyloid fibrils contain proteins that interlock like the teeth of a zipper. The researchers also reported their hypothesis that this dry molecular zipper is in the fibrils that form in Alzheimer’s disease, as well as in Parkinson’s disease and two dozen other degenerative diseases. Their hypothesis has been supported by recent studies.

Alzheimer’s disease, the most common cause of dementia among older adults, is an irreversible, progressive brain disorder that kills brain cells, gradually destroys memory and eventually affects thinking, behavior and the ability to carry out the daily tasks of life. More than 5.5 million Americans, most of whom are over 65, are thought to have dementia caused by Alzheimer’s.

The UCLA team reports in the journal Nature Communications that the small protein beta amyloid, also known as a peptide, that plays an important role in Alzheimer’s has a normal version that may be less harmful than previously thought and an age-damaged version that is more harmful.

Rebeccah Warmack, who was a UCLA graduate student at the time of the study and is its lead author, discovered that a specific version of age-modified beta amyloid contains a second molecular zipper not previously known to exist. Proteins live in water, but all the water gets pushed out as the fibril is sealed and zipped up. Warmack worked closely with UCLA graduate students David Boyer, Chih-Te Zee and Logan Richards; as well as senior research scientists Michael Sawaya and Duilio Cascio.

What goes wrong with beta amyloid, whose most common forms have 40 or 42 amino acids that are connected like a string of beads on a necklace?

The researchers report that with age, the 23rd amino acid can spontaneously form a kink, similar to one in a garden hose. This kinked form is known as isoAsp23. The normal version does not create the stronger second molecular zipper, but the kinked form does.

“Now we know a second water-free zipper can form, and is extremely difficult to pry apart,” Warmack said. “We don’t know how to break the zipper.”

The normal form of beta amyloid has six water molecules that prevent the formation of a tight zipper, but the kink ejects these water molecules, allowing the zipper to form.

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green. Photo credit: Rebeccah Warmack/UCLA

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green.
“Rebeccah has shown this kink leads to faster growth of the fibrils that have been linked to Alzheimer’s disease,” said Clarke, who has conducted research on biochemistry of the brain and Alzheimer’s disease since 1990. “This second molecular zipper is double trouble. Once it’s zipped, it’s zipped, and once the formation of fibrils starts, it looks like you can’t stop it. The kinked form initiates a dangerous cascade of events that we believe can result in Alzheimer’s disease.”

Why does beta amyloid’s 23rd amino acid sometimes form this dangerous kink?

Clarke thinks the kinks in this amino acid form throughout our lives, but we have a protein repair enzyme that fixes them.

“As we get older, maybe the repair enzyme misses the repair once or twice,” he said. “The repair enzyme might be 99.9% effective, but over 60 years or more, the kinks eventually build up. If not repaired or if degraded in time, the kink can spread to virtually every neuron and can do tremendous damage.”

“The good news is that knowing what the problem is, we can think about ways to solve it,” he added. “This kinked amino acid is where we want to look.”

The research offers clues to pharmaceutical companies, which could develop ways to prevent formation of the kink or get the repair enzyme to work better; or by designing a cap that would prevent fibrils from growing.

Clarke said beta amyloid and a much larger protein tau — with more than 750 amino acids — make a devastating one-two punch that forms fibrils and spreads them to many neurons throughout the brain. All humans have both beta amyloid and tau. Researchers say it appears that beta amyloid produces fibrils that can lead to tau aggregates, which can spread the toxicity to other brain cells. However, exactly how beta amyloid and tau work together to kill neurons is not yet known.

In this study, Warmack produced crystals, both the normal and kinked types, in 15 of beta amyloid’s amino acids. She used a modified type of cryo-electron microscopy to analyze the crystals. Cryo-electron microscopy, whose development won its creators the 2017 Nobel Prize in chemistry, enables scientists to see large biomolecules in extraordinary detail. Professor Tamir Gonen pioneered the modified microscopy, called microcrystal electron diffraction, which enables scientists to study biomolecules of any size.

Eisenberg is UCLA’s Paul D. Boyer Professor of Molecular Biology and a Howard Hughes Medical Institute investigator. Other researchers are co-author Gonen, a professor of biological chemistry and physiology at the UCLA David Geffen School of Medicine and a Howard Hughes Medical Institute investigator; and Jose Rodriguez, assistant professor of chemistry and biochemistry who holds the Howard Reiss Career Development Chair.

The research was funded by the National Science Foundation, National Institutes of Health, Howard Hughes Medical Institute, and the UCLA Longevity Center’s Elizabeth and Thomas Plott Chair in Gerontology, which Clarke held for five years.

This article originally appeared in the UCLA Newsroom.

Einstein’s general relativity theory is questioned but still stands ‘for now,’ team reports

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Photo of artist rendering of SO-2 star.

A star known as S0-2 (the blue and green object in this artist’s rendering) made its closest approach to the supermassive black hole at the center of the Milky Way in 2018. Artist’s rendering by Nicolle Fuller/National Science Foundation.

More than 100 years after Albert Einstein published his iconic theory of general relativity, it is beginning to fray at the edges, said Andrea Ghez, UCLA professor of physics and astronomy. Now, in the most comprehensive test of general relativity near the monstrous black hole at the center of our galaxy, Ghez and her research team report July 25 in the journal Science that Einstein’s theory of general relativity holds up.

“Einstein’s right, at least for now,” said Ghez, a co-lead author of the research. “We can absolutely rule out Newton’s law of gravity. Our observations are consistent with Einstein’s theory of general relativity. However, his theory is definitely showing vulnerability. It cannot fully explain gravity inside a black hole, and at some point we will need to move beyond Einstein’s theory to a more comprehensive theory of gravity that explains what a black hole is.”

Einstein’s 1915 theory of general relativity holds that what we perceive as the force of gravity arises from the curvature of space and time. The scientist proposed that objects such as the sun and the Earth change this geometry. Einstein’s theory is the best description of how gravity works, said Ghez, whose UCLA-led team of astronomers has made direct measurements of the phenomenon near a supermassive black hole — research Ghez describes as “extreme astrophysics.”

The laws of physics, including gravity, should be valid everywhere in the universe, said Ghez, who added that her research team is one of only two groups in the world to watch a star known as S0-2 make a complete orbit in three dimensions around the supermassive black hole at the center of the Milky Way. The full orbit takes 16 years, and the black hole’s mass is about 4 million times that of the sun.

The researchers say their work is the most detailed study ever conducted into the supermassive black hole and Einstein’s theory of general relativity.

The key data in the research were spectra that Ghez’s team analyzed last April, May and September as her “favorite star” made its closest approach to the enormous black hole. Spectra, which Ghez described as the “rainbow of light” from stars, show the intensity of light and offer important information about the star from which the light travels. Spectra also show the composition of the star. These data were combined with measurements Ghez and her team have made over the last 24 years.

Spectra — collected at the W.M. Keck Observatory in Hawaii using a spectrograph built at UCLA by a team led by colleague James Larkin — provide the third dimension, revealing the star’s motion at a level of precision not previously attained. (Images of the star the researchers took at the Keck Observatory provide the two other dimensions.) Larkin’s instrument takes light from a star and disperses it, similar to the way raindrops disperse light from the sun to create a rainbow, Ghez said.

“What’s so special about S0-2 is we have its complete orbit in three dimensions,” said Ghez, who holds the Lauren B. Leichtman and Arthur E. Levine Chair in Astrophysics. “That’s what gives us the entry ticket into the tests of general relativity. We asked how gravity behaves near a supermassive black hole and whether Einstein’s theory is telling us the full story. Seeing stars go through their complete orbit provides the first opportunity to test fundamental physics using the motions of these stars.”

Ghez’s research team was able to see the co-mingling of space and time near the supermassive black hole. “In Newton’s version of gravity, space and time are separate, and do not co-mingle; under Einstein, they get completely co-mingled near a black hole,” she said.

“Making a measurement of such fundamental importance has required years of patient observing, enabled by state-of-the-art technology,” said Richard Green, director of the National Science Foundation’s division of astronomical sciences. For more than two decades, the division has supported Ghez, along with several of the technical elements critical to the research team’s discovery. “Through their rigorous efforts, Ghez and her collaborators have produced a high-significance validation of Einstein’s idea about strong gravity.”

Keck Observatory Director Hilton Lewis called Ghez “one of our most passionate and tenacious Keck users.” “Her latest groundbreaking research,” he said, “is the culmination of unwavering commitment over the past two decades to unlock the mysteries of the supermassive black hole at the center of our Milky Way galaxy.”

The researchers studied photons — particles of light — as they traveled from S0-2 to Earth. S0-2 moves around the black hole at blistering speeds of more than 16 million miles per hour at its closest approach. Einstein had reported that in this region close to the black hole, photons have to do extra work. Their wavelength as they leave the star depends not only on how fast the star is moving, but also on how much energy the photons expend to escape the black hole’s powerful gravitational field. Near a black hole, gravity is much stronger than on Earth.

Ghez was given the opportunity to present partial data last summer, but chose not to so that her team could thoroughly analyze the data first. “We’re learning how gravity works. It’s one of four fundamental forces and the one we have tested the least,” she said. “There are many regions where we just haven’t asked, how does gravity work here? It’s easy to be overconfident and there are many ways to misinterpret the data, many ways that small errors can accumulate into significant mistakes, which is why we did not rush our analysis.”

Ghez, a 2008 recipient of the MacArthur “Genius” Fellowship, studies more than 3,000 stars that orbit the supermassive black hole. Hundreds of them are young, she said, in a region where astronomers did not expect to see them.

It takes 26,000 years for the photons from S0-2 to reach Earth. “We’re so excited, and have been preparing for years to make these measurements,” said Ghez, who directs the UCLA Galactic Center Group. “For us, it’s visceral, it’s now — but it actually happened 26,000 years ago!”

This is the first of many tests of general relativity Ghez’s research team will conduct on stars near the supermassive black hole. Among the stars that most interest her is S0-102, which has the shortest orbit, taking 11 1/2 years to complete a full orbit around the black hole. Most of the stars Ghez studies have orbits of much longer than a human lifespan.

Ghez’s team took measurements about every four nights during crucial periods in 2018 using the Keck Observatory — which sits atop Hawaii’s dormant Mauna Kea volcano and houses one of the world’s largest and premier optical and infrared telescopes. Measurements are also taken with an optical-infrared telescope at Gemini Observatory and Subaru Telescope, also in Hawaii. She and her team have used these telescopes both on site in Hawaii and remotely from an observation room in UCLA’s department of physics and astronomy.

Black holes have such high density that nothing can escape their gravitational pull, not even light. (They cannot be seen directly, but their influence on nearby stars is visible and provides a signature. Once something crosses the “event horizon” of a black hole, it will not be able to escape. However, the star S0-2 is still rather far from the event horizon, even at its closest approach, so its photons do not get pulled in.)

Photo of telescope pointing to the sky.

Lasers from the two Keck telescopes point in the direction of the center of our galaxy. Each laser creates an “artificial star” that astronomers can use to correct for the blurring caused by the Earth’s atmosphere. Photo: Ethan Tweedie

Ghez’s co-authors include Tuan Do, lead author of the Science paper, a UCLA research scientist and deputy director of the UCLA Galactic Center Group; Aurelien Hees, a former UCLA postdoctoral scholar, now a researcher at the Paris Observatory; Mark Morris, UCLA professor of physics and astronomy; Eric Becklin, UCLA professor emeritus of physics and astronomy; Smadar Naoz, UCLA assistant professor of physics and astronomy; Jessica Lu, a former UCLA graduate student who is now a UC Berkeley assistant professor of astronomy; UCLA graduate student Devin Chu; Greg Martinez, UCLA project scientist; Shoko Sakai, a UCLA research scientist; Shogo Nishiyama, associate professor with Japan’s Miyagi University of Education; and Rainer Schoedel, a researcher with Spain’s Instituto de Astrofısica de Andalucıa.

The National Science Foundation has funded Ghez’s research for the last 25 years. More recently, her research has also been supported by the W.M. Keck Foundation, the Gordon and Betty Moore Foundation and the Heising-Simons Foundation; as well as Lauren Leichtman and Arthur Levine, and Howard and Astrid Preston.

In 1998, Ghez answered one of astronomy’s most important questions, helping to show that a supermassive black hole resides at the center of our Milky Way galaxy. The question had been a subject of much debate among astronomers for more than a quarter of a century.

A powerful technology that Ghez helped to pioneer, called adaptive optics, corrects the distorting effects of the Earth’s atmosphere in real time. With adaptive optics at Keck Observatory, Ghez and her colleagues have revealed many surprises about the environments surrounding supermassive black holes. For example, they discovered young stars where none was expected to be seen and a lack of old stars where many were anticipated. It’s unclear whether S0-2 is young or just masquerading as a young star, Ghez said.

In 2000, she and colleagues reported that for the first time, astronomers had seen stars accelerate around the supermassive black hole. In 2003, Ghez reported that the case for the Milky Way’s black hole had been strengthened substantially and that all of the proposed alternatives could be excluded.

In 2005, Ghez and her colleagues took the first clear picture of the center of the Milky Way, including the area surrounding the black hole, at Keck Observatory. And in 2017, Ghez’s research team reported that S0-2 does not have a companion star, solving another mystery.

This article originally appeared in the UCLA Newsroom.

Study finds cultural differences in attitudes toward infidelity, jealousy

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Photo of father and small son.

The 11 societies studied included the Namibian community of the Himba, where this father and child live. Photo credit: Brooke Scelza.

In cultures where fathers are highly invested in the care of their children, both men and women respond more negatively to the idea of infidelity, a cross-cultural study led by UCLA professor of anthropology Brooke Scelza found.

Jealousy is a well-examined human phenomenon that women and men often experience differently, but the study published this week in Nature Human Behavior also examined cultural differences in the experience of jealousy, by surveying 1,048 men and women from 11 societies on five continents.

Scelza wanted to use established evolutionary science to go beyond the idea that a phenomenon of human behavior is either universal or variable.

“In studying jealousy we find evidence for both,” she said. “Almost everywhere men tend to be more upset than women by sexual infidelity,” she said. “At the same time, cultural factors lead to population-level differences in how infidelity is viewed.”

For example, in places where men are not expected to be as involved in day-to-day care of children, people were less prone to jealousy. And in cultures that are more accepting of what Scelza describes as “concurrent” sexual relationships, responses to questions about jealousy were more muted.

The study harnessed expertise from a dozen researchers who have worked extensively in the populations surveyed. Eight were small-scale societies, including the Himba, a pastoral community in Namibia, and the Tismane, indigenous people of Bolivia. Three populations of respondents were from urban settings, such as Los Angeles, India and Okinawa, Japan.

Researchers used a five-point scale to determine attitudes about infidelity and jealousy.

“Very few people of either sex said that either sexual or emotional infidelity was ‘very good’ but responses of ‘OK’ and ‘good’ were not uncommon,” Scelza said. “What is most interesting is that we were able to not just show that cross-cultural variation in jealous response exists, which by itself is not very surprising, but we were able to explain some of that variation using principles from evolutionary theory about the relative costs and benefits of infidelity, including how common extramarital sex is, and whether men are very involved in child-rearing.”

Another surprising finding of the study was that in the majority of populations studied, both men and women found sexual infidelity more upsetting than emotional infidelity. In only four of the populations, including Los Angeles and Okinawa, a majority of women responded that emotional infidelity was more upsetting. These responses echoed what women surveyed in smaller communities like the Himba and Tsimane reported to researchers — that sexual infidelity leads to fears of loss of paternal support and resources for children.

“Typically, we tend to think that emotional infidelity is more likely to lead to loss of resources, which is why it is thought to be more upsetting to women, but we found the opposite,” Scelza said.

This study is part of a growing body of work over the last decade from social scientists who seek to be more inclusive and not just focus their research on western, educated, industrial, rich and democratic — also known as WEIRD — societies, Scelza said.

“For a long time in psychology there was a tendency to use student samples from U.S. and European universities, and if they found a consistent result, extrapolate that as something that could be a ‘human universal,’” she said. “But there are many reasons to believe that people from WEIRD populations are unlikely to be representative of humanity more generally.”

For example, Scelza’s idea for the study was sparked by her ongoing work with Himba pastoralists living in rural Namibia. In her work on marital and family dynamics she found that both women and men frequently had multiple concurrent sexual partners but still experienced happy marriages.

“Over and over I was told that one could love both their husband and another man, and that in fact, many people would be uninterested in having a spouse who could not attract other partners,” she said. “It made me wonder whether or not people in this culture experienced jealousy at all. It turns out they do, but those findings inspired me to take a broader look at how jealousy is treated around the world, and try to understand where and why people view it differently.”

This article originally appeared in the UCLA Newsroom.