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Two key brain systems are central to psychosis, Stanford Medicine-led study finds

When the brain has trouble filtering incoming information and predicting what’s likely to happen, psychosis can result, Stanford Medicine-led research shows.

April 11, 2024 - By Erin Digitale

People with psychosis have trouble filtering relevant information (mesh funnel) and predicting rewarding events (broken crystal ball), creating a complex inner world. Emily Moskal

Inside the brains of people with psychosis, two key systems are malfunctioning: a “filter” that directs attention toward important external events and internal thoughts, and a “predictor” composed of pathways that anticipate rewards.

Dysfunction of these systems makes it difficult to know what’s real, manifesting as hallucinations and delusions. 

The findings come from a Stanford Medicine-led study , published April 11 in  Molecular Psychiatry , that used brain scan data from children, teens and young adults with psychosis. The results confirm an existing theory of how breaks with reality occur.

“This work provides a good model for understanding the development and progression of schizophrenia, which is a challenging problem,” said lead author  Kaustubh Supekar , PhD, clinical associate professor of psychiatry and behavioral sciences.

The findings, observed in individuals with a rare genetic disease called 22q11.2 deletion syndrome who experience psychosis as well as in those with psychosis of unknown origin, advance scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis.

During psychosis, patients experience hallucinations, such as hearing voices, and hold delusional beliefs, such as thinking that people who are not real exist. Psychosis can occur on its own and isa hallmark of certain serious mental illnesses, including bipolar disorder and schizophrenia. Schizophrenia is also characterized by social withdrawal, disorganized thinking and speech, and a reduction in energy and motivation.

It is challenging to study how schizophrenia begins in the brain. The condition usually emerges in teens or young adults, most of whom soon begin taking antipsychotic medications to ease their symptoms. When researchers analyze brain scans from people with established schizophrenia, they cannot distinguish the effects of the disease from the effects of the medications. They also do not know how schizophrenia changes the brain as the disease progresses. 

To get an early view of the disease process, the Stanford Medicine team studied young people aged 6 to 39 with 22q11.2 deletion syndrome, a genetic condition with a 30% risk for psychosis, schizophrenia or both. 

Kaustubh Supekar

Brain function in 22q11.2 patients who have psychosis is similar to that in people with psychosis of unknown origin, they found. And these brain patterns matched what the researchers had previously theorized was generating psychosis symptoms.

“The brain patterns we identified support our theoretical models of how cognitive control systems malfunction in psychosis,” said senior study author  Vinod Menon , PhD, the Rachael L. and Walter F. Nichols, MD, Professor; a professor of psychiatry and behavioral sciences; and director of the  Stanford Cognitive and Systems Neuroscience Laboratory .

Thoughts that are not linked to reality can capture the brain’s cognitive control networks, he said. “This process derails the normal functioning of cognitive control, allowing intrusive thoughts to dominate, culminating in symptoms we recognize as psychosis.”

Cerebral sorting  

Normally, the brain’s cognitive filtering system — aka the salience network — works behind the scenes to selectively direct our attention to important internal thoughts and external events. With its help, we can dismiss irrational thoughts and unimportant events and focus on what’s real and meaningful to us, such as paying attention to traffic so we avoid a collision.

The ventral striatum, a small brain region, and associated brain pathways driven by dopamine, play an important role in predicting what will be rewarding or important. 

For the study, the researchers assembled as much functional MRI brain-scan data as possible from young people with 22q11.2 deletion syndrome, totaling 101 individuals scanned at three different universities. (The study also included brain scans from several comparison groups without 22q11.2 deletion syndrome: 120 people with early idiopathic psychosis, 101 people with autism, 123 with attention deficit/hyperactivity disorder and 411 healthy controls.) 

The genetic condition, characterized by deletion of part of the 22nd chromosome, affects 1 in every 2,000 to 4,000 people. In addition to the 30% risk of schizophrenia or psychosis, people with the syndrome can also have autism or attention deficit hyperactivity disorder, which is why these conditions were included in the comparison groups.

The researchers used a type of machine learning algorithm called a spatiotemporal deep neural network to characterize patterns of brain function in all patients with 22q11.2 deletion syndrome compared with healthy subjects. With a cohort of patients whose brains were scanned at the University of California, Los Angeles, they developed an algorithmic model that distinguished brain scans from people with 22q11.2 deletion syndrome versus those without it. The model predicted the syndrome with greater than 94% accuracy. They validated the model in additional groups of people with or without the genetic syndrome who had received brain scans at UC Davis and Pontificia Universidad Católica de Chile, showing that in these independent groups, the model sorted brain scans with 84% to 90% accuracy.

The researchers then used the model to investigate which brain features play the biggest role in psychosis. Prior studies of psychosis had not given consistent results, likely because their sample sizes were too small. 

Vinod Menon

Comparing brain scans from 22q11.2 deletion syndrome patients who had and did not have psychosis, the researchers showed that the brain areas contributing most to psychosis are the anterior insula (a key part of the salience network or “filter”) and the ventral striatum (the “reward predictor”); this was true for different cohorts of patients.

In comparing the brain features of people with 22q11.2 deletion syndrome and psychosis against people with psychosis of unknown origin, the model found significant overlap, indicating that these brain features are characteristic of psychosis in general.

A second mathematical model, trained to distinguish all subjects with 22q11.2 deletion syndrome and psychosis from those who have the genetic syndrome but without psychosis, selected brain scans from people with idiopathic psychosis with 77.5% accuracy, again supporting the idea that the brain’s filtering and predicting centers are key to psychosis.

Furthermore, this model was specific to psychosis: It could not classify people with idiopathic autism or ADHD.

“It was quite exciting to trace our steps back to our initial question — ‘What are the dysfunctional brain systems in schizophrenia?’ — and to discover similar patterns in this context,” Menon said. “At the neural level, the characteristics differentiating individuals with psychosis in 22q11.2 deletion syndrome are mirroring the pathways we’ve pinpointed in schizophrenia. This parallel reinforces our understanding of psychosis as a condition with identifiable and consistent brain signatures.” However, these brain signatures were not seen in people with the genetic syndrome but no psychosis, holding clues to future directions for research, he added.

Applications for treatment or prevention

In addition to supporting the scientists’ theory about how psychosis occurs, the findings have implications for understanding the condition — and possibly preventing it.

“One of my goals is to prevent or delay development of schizophrenia,” Supekar said. The fact that the new findings are consistent with the team’s prior research on which brain centers contribute most to schizophrenia in adults suggests there may be a way to prevent it, he said. “In schizophrenia, by the time of diagnosis, a lot of damage has already occurred in the brain, and it can be very difficult to change the course of the disease.”

“What we saw is that, early on, functional interactions among brain regions within the same brain systems are abnormal,” he added. “The abnormalities do not start when you are in your 20s; they are evident even when you are 7 or 8.”

Our discoveries underscore the importance of approaching people with psychosis with compassion.

The researchers plan to use existing treatments, such as transcranial magnetic stimulation or focused ultrasound, targeted at these brain centers in young people at risk of psychosis, such as those with 22q11.2 deletion syndrome or with two parents who have schizophrenia, to see if they prevent or delay the onset of the condition or lessen symptoms once they appear. 

The results also suggest that using functional MRI to monitor brain activity at the key centers could help scientists investigate how existing antipsychotic medications are working. 

Although it’s still puzzling why someone becomes untethered from reality — given how risky it seems for one’s well-being — the “how” is now understandable, Supekar said. “From a mechanistic point of view, it makes sense,” he said.

“Our discoveries underscore the importance of approaching people with psychosis with compassion,” Menon said, adding that his team hopes their work not only advances scientific understanding but also inspires a cultural shift toward empathy and support for those experiencing psychosis. 

“I recently had the privilege of engaging with individuals from our department’s early psychosis treatment group,” he said. “Their message was a clear and powerful: ‘We share more similarities than differences. Like anyone, we experience our own highs and lows.’ Their words were a heartfelt appeal for greater empathy and understanding toward those living with this condition. It was a call to view psychosis through a lens of empathy and solidarity.”

Researchers contributed to the study from UCLA, Clinica Alemana Universidad del Desarrollo, Pontificia Universidad Católica de Chile, the University of Oxford and UC Davis.

The study was funded by the Stanford Maternal and Child Health Research Institute’s Uytengsu-Hamilton 22q11 Neuropsychiatry Research Program, FONDEYCT (the National Fund for Scientific and Technological Development of the government of Chile), ANID-Chile (the Chilean National Agency for Research and Development) and the U.S. National Institutes of Health (grants AG072114, MH121069, MH085953 and MH101779).

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Heat-Related E.R. Visits Rose in 2023, C.D.C. Study Finds

By Noah Weiland

Reporting from Washington

The rate of emergency room visits caused by heat illness increased significantly last year in large swaths of the country compared with the previous five years, according to a study published on Thursday by the Centers for Disease Control and Prevention.

The research, which analyzed visits during the warmer months of the year, offers new insight into the medical consequences of the record-breaking heat recorded across the country in 2023 as sweltering temperatures stretched late into the year.

What the Numbers Say: People in the South were especially affected by serious heat illness.

The researchers used data on emergency room visits from an electronic surveillance program used by states and the federal government to detect the spread of diseases. They compiled the number of heat-related emergency room visits in different regions of the country and compared them to data from the previous five years.

Nearly 120,000 heat-related emergency room visits were recorded in the surveillance program last year, with more than 90 percent of them occurring between May and September, the researchers found.

The highest rate of visits occurred in a region encompassing Arkansas, Louisiana, New Mexico, Oklahoma and Texas. Overall, the study also found that men and people between the ages of 18 and 64 had higher rates of visits.

How It Happens: Heat can be a silent killer, experts and health providers say.

Last year was the warmest on Earth in a century and a half, with the hottest summer on record . Climate scientists have attributed the trend in part to greenhouse gas emissions and their effects on global warming, and they have warned that the timing of a shift in tropical weather patterns last year could foreshadow an even hotter 2024.

Heat illness often occurs gradually over the course of hours, and it can cause major damage to the body’s organs . Early symptoms of heat illness can include fatigue, dehydration, nausea, headache, increased heart rate and muscle spasms.

People do not typically think of themselves as at high risk of succumbing to heat or at greater risk than they once were, causing them to underestimate how a heat wave could lead them to the emergency room, said Kristie L. Ebi, a professor at the University of Washington who is an expert on the health risks of extreme heat.

“The heat you were asked to manage 10 years ago is not the heat you’re being asked to manage today,” she said. One of the first symptoms of heat illness can be confusion, she added, making it harder for someone to respond without help from others.

What Happens Next: States and hospitals are gearing up for another summer of extreme heat.

Dr. Srikanth Paladugu, an epidemiologist at the New Mexico Department of Health, said the state had nearly 450 heat-related emergency room visits in July last year alone and over 900 between April and September, more than double the number recorded during that stretch in 2019.

In preparation for this year’s warmer months, state officials are working to coordinate cooling shelters and areas where people can be splashed by water, Dr. Paladugu said.

Dr. Aneesh Narang, an emergency medicine physician at Banner-University Medical Center in Phoenix, said he often saw roughly half a dozen heat stroke cases a day last summer, including patients with body temperatures of 106 or 107 degrees. Heat illness patients require enormous resources, he added, including ice packs, fans, misters and cooling blankets.

“There’s so much that has to happen in the first few minutes to give that patient a chance for survival,” he said.

Dr. Narang said hospital employees had already begun evaluating protocols and working to ensure that there are enough supplies to contend with the expected number of heat illness patients this year.

“Every year now we’re doing this earlier and earlier,” he said. “We know that the chances are it’s going to be the same or worse.”

Noah Weiland writes about health care for The Times. More about Noah Weiland

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Rise and grind working late, volatile hours may lead to depression, illness by 50.

Ronnie Cohen

Working late nights and variable schedules when you're young is linked with poor health and depression at 50, a new study finds. simonkr/Getty Images hide caption

Working late nights and variable schedules when you're young is linked with poor health and depression at 50, a new study finds.

Feeling burned out and looking for reasons to work less? A new study shows that working nights and volatile schedules in young adulthood can leave you vulnerable to depression and poor health in middle age.

The research examined the work schedules and sleep patterns of more than 7,000 Americans interviewed over three decades, from the ages of 22 through 50. To the surprise of the study's author, NYU Silver School of Social Work professor Wen-Jui Han , only one-quarter of the participants worked exclusively traditional daytime hours.

The remainder – three-quarters of the sample of American workers born in the 1960s – worked variable hours. Those with more volatile work schedules, including night hours and rotating shifts, reported less sleep and a greater likelihood of poor health and depression at age 50 than those with more stable schedules and daytime hours.

"Our work now is making us sick and poor," Han said in a Zoom interview. "Work is supposed to allow us to accumulate resources. But, for a lot of people, their work doesn't allow them to do so. They actually become more and more miserable over time."

Han would like her research — published last week in PLOS One — to prompt conversations about ways to "provide resources to support people to have a happy and healthy life when they're physically exhausted and emotionally drained because of their work."

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She was one of those employees. In her 40s, when Han was up for tenure, she worked 16-hour days, taking time off only to eat and sleep, though not sleeping nearly enough. Her doctor warned her that her physical condition appeared more like that of a woman in her 60s.

She was overworking like many young professionals who have embraced hustle culture and work around the clock.

"We can say they voluntarily want to work long hours, but in reality, it's not about voluntarily working long hours," Han said. "They sense that the culture of their work demands that they work long hours, or they may get penalized."

She says the participants in her study who sacrificed sleep to earn a living, suffered depression and poor health, she said. "When our work becomes a daily stressor, these are the kind of health consequences you may expect to see 30 years down the road."

Black men and women and workers with limited educations disproportionately shouldered the burden of night shifts, volatile work schedules and sleep deprivation, the study shows.

White college-educated women with stable daytime work reported an average of six more hours of sleep a week than Black men who had not completed high school and who worked variable hours for most of their lives, Han's study found.

And Black women who did not complete high school and switched from regular daytime hours to volatile employment in their 30s were four times more likely to report poor health than white college-educated men with stable and standard daytime work lives.

The study shows a relationship between working nights and rotating shifts with poor sleep and poor health, but it cannot prove one caused the other. That said, the U.S. Centers for Disease Control and Prevention links insufficient sleep with chronic diseases, such as diabetes, heart disease and obesity, and African Americans are more likely than whites to suffer from these diseases.

How much a person needs to sleep to remain healthy depends upon age, but the American Academy of Sleep Medicine and the Sleep Research Society recommend that adults between 18 and 60 years old get at least seven hours of shut-eye a night.

Dr. Alyson Myers appreciated the new study's focus on the connection between work schedules, sleep and poor health.

The study findings confirmed what she sees in many of her diabetes patients, who often get no more than five hours of sleep after they work night shifts. She counsels them to try to switch to days, and when they do, their health improves, the endocrinologist and professor at the Albert Einstein College of Medicine said.

Prior research has shown that sleep, diet and social habits required to work nights and rotating shifts, can increase the risk of developing diabetes. In 2019, Blacks were twice as likely as whites to die of diabetes , according to the U.S. Department of Health and Human Services.

"Poor sleep is a risk factor for diabetes that very often we do not talk about," said Myers, who was not involved in the study. "One of the things that I have to preach to my patients about is that working nights, and if you get only four or five or less hours of sleep, that's going to increase your risk of diabetes and also worsen your glycemic control."

One patient was angry with her when he followed her advice, switched from working nights to days and as a result had to contend with commute traffic. "But," she said in a Zoom interview, "we actually got better control of his blood sugar when he switched to working the day shift."

About 16% of American workers were employed outside of daytime hours in 2019, according to the U.S. Bureau of Labor Statistics.

Many of the participants in Hans' study who had volatile work schedules tended to have part-time jobs, in some cases multiple part-time jobs. "Unfortunately," Myers said, "the trend for a lot of these people is that they have to work more than one job to survive."

Ronnie Cohen is a San Francisco Bay Area journalist focused on health and social justice issues.

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Nearly 170 genes determine hair, skin and eye color, CRISPR study reveals

Black hair? Green eyes? More than 160 genes determine your coloration, and their interactions are incredibly complicated.

Human skin , hair, and eyes come in a huge variety of colors, but until now, scientists have only known a fraction of the genetic diversity driving this variation. Now, new research finds many dozens of genes that may produce this broad diversity. 

In a genome-wide screening, researchers pinpointed 169 genes that are likely involved in human pigmentation, including 135 previously not known to play a role. Because of the wide distribution of pigments within the human body, some of these genes might be involved in disorders such as the skin cancer melanoma and even Parkinson's disease , which affects pigmented cells in a region of the brain important for movement, the study authors reported. 

"Pigmentation by itself is interesting both in the context of human variation and evolution, but also in the context of disease," study leader Joanna Wysocka , a developmental biologist at Stanford University and the Howard Hughes Medical Institute, told Live Science. 

Related: 10 common skin conditions

The diversity of coloration

Humans get their skin, eye and hair colors from a pigment called melanin, which comes in a brown-and-black form, called eumelanin, and a yellow-and-red form, called pheomelanin. How much of each melanin type is expressed, and in what balance, determines whether someone will have, for example, jet-black hair or fiery-red locks, and the same goes for skin tone and eye color. (The more melanin in the eye, the darker it is. People with blue eyes lack melanin in the iris, while people with green eyes have it in only one layer.)

Cells called melanocytes make melanin, but the difference in a dark-featured person and a light-featured person isn't in the number of melanocytes but in how much melanin those melanocytes produce, Wysocka said.

Previous studies had revealed some genes behind melanocyte maturation and melanin production, but only enough to explain between 23% and 35% of the variation in human skin color, Wysocka and her team wrote Thursday (Aug. 10) in the journal Science . To find out which other genes might contribute to human pigmentation, the researchers conducted a whole-genome study.

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First, they had to differentiate high- and low-melanin melanocytes. To do so, they sorted cells in lab dishes, using the light-scattering properties of melanin, which describe how light behaves when it strikes the pigment. This new method, which involves shining fluorescent light on cells flowing through a channel, efficiently sorted both human melanocyte cells and melanoma cells, a cancerous version of melanocytes, by their melanin levels.

Next, the researchers used CRISPR-Cas9 gene-editing technology to systematically go into cells and mutate every gene, one at a time. If the broken gene was associated with melanin production or melanocyte maturation, the team reasoned, pigment levels in the melanocyte would fall and then be detected by the sorting tool.

This method returned the list of 169 genes, whose activity levels the researchers then checked in real human tissue — in this case, samples of infant foreskin donated after circumcisions. They found that nearly 70% of the genes were more active in babies with darker skin tones than in those with lighter skin tones.

Protective pigments

Not every gene necessarily drives melanin production, Wysocka said. While some determine how melanocytes mature and how much pigment they make, others are likely involved in a more peripheral way.

The genes largely fell into two categories: One group helped regulate genes, while the other influenced endosome trafficking. Endosomes are tiny transport packets within cells that shuttle materials around. The researchers closely analyzed one gene from each group and discovered that one was involved in the maturation of melanosomes, the tiny cellular organs that make and store the pigment within melanocytes. The other regulates the pH of the melanosomes, ensuring that the enzymes that piece together the pigments can function properly, Wysocka said.

— Why does hair turn gray?

— What if humans had photosynthetic skin?

— Why do we grow more hair on our heads than on our bodies?

Melanin isn't just ornamental; it protects the skin and eyes from sun damage. It also shows up in the brain in a structure called the substantia nigra, whose name means "black substance." The structure's high melanin content protects cells from reactive molecules, but in Parkinson's disease, substantia nigra cells die off, and thus melanin declines.

"It's an interesting question whether some of these pathways we have identified in melanocytes will also be important for neuroprotection in the brain," Wysocka said.

Stephanie Pappas is a contributing writer for Live Science, covering topics ranging from geoscience to archaeology to the human brain and behavior. She was previously a senior writer for Live Science but is now a freelancer based in Denver, Colorado, and regularly contributes to Scientific American and The Monitor, the monthly magazine of the American Psychological Association. Stephanie received a bachelor's degree in psychology from the University of South Carolina and a graduate certificate in science communication from the University of California, Santa Cruz. 

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Why Engineers Should Study Philosophy

• Marco Argenti

Understanding the “why” before you start working on the “how” is a critical skill — especially in the age of AI.

The ability to develop crisp mental models around the problems you want to solve and understanding the why before you start working on the how is an increasingly critical skill, especially in the age of AI. Coding is one of the things AI does best and its capabilities are quickly improving. However, there’s a catch: Code created by an AI can be syntactically and semantically correct but not functionally correct. In other words, it can work well, but not do what you want it to do. Having a crisp mental model around a problem, being able to break it down into steps that are tractable, perfect first-principle thinking, sometimes being prepared (and able to) debate a stubborn AI — these are the skills that will make a great engineer in the future, and likely the same consideration applies to many job categories.

I recently told my daughter, a college student: If you want to pursue a career in engineering, you should focus on learning philosophy in addition to traditional engineering coursework. Why? Because it will improve your code.

• MA Marco Argenti is the Chief Information Officer at Goldman Sachs.

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Most LGBTQ Americans experience harassment, discrimination, Harvard study finds

The majority of LGBTQ Americans say they have experienced some form of harassment or discrimination due to their sexual orientation or gender identity, according to a report by the Harvard T.H. Chan School of Public Health, the Robert Wood Johnson Foundation and National Public Radio.

The survey , a nationally representative sample of 489 lesbian, gay, bisexual, transgender and queer adults, found that more than half of them experienced slurs (57 percent) or offensive comments (53 percent). Most of those surveyed also reported that they or an LGBTQ friend or family member has been threatened or harassed (57 percent), sexually harassed (51 percent) or has experienced violence (51 percent) on the basis of their sexuality or gender identity.

"LGBTQ people’s day-to-day experiences are still structured by discrimination, harassment and prejudice."

Logan S. Casey

Harvard researcher Logan S. Casey, who was part of the report's research team, said what sets this survey apart from previous ones is its focus on the day-to-day experience of discrimination for LGBTQ people.

“Lots of work has been done about what people think about discrimination in America. This [survey] goes into great detail about people’s personal experiences of discrimination across many areas of life,” Casey explained.

For Casey, one of the most important findings is “how pervasive people’s experiences of violence and harassment are.” For example, a third of LGBTQ Americans report that they or an LGBTQ friend or family member has experienced verbal harassment while using a bathroom.

“LGBTQ people’s day-to-day experiences are still structured by discrimination, harassment and prejudice,” Casey said.

Institutional Discrimination

In addition to individual slights and aggressions, the report noted large portions of LGBTQ people confront institutional discrimination. At least one in five of those surveyed said they have been discriminated against in the process of applying for a job (20 percent), being paid equally or considered for a promotion (22 percent) or buying or renting a home (22 percent), the survey found.

In terms of education, among those in the LGBTQ community who applied for or attended college, 20 percent said they had experienced discrimination because of their gender identity or sexual orientation while applying or while at college.

feature Facebook can tell if you're gay based on a few 'likes,' study says

The discrimination extends to the political sphere as well. One in 10 LGBTQ people said “they have been personally discriminated against because they are LGBTQ when trying to vote or participate in politics.”

Those surveyed also reported avoiding situations in which they may encounter discrimination.

“Roughly one in six LGBTQ people say they have avoided medical care (18 percent) and calling the police (15 percent), even when in need, due to concern that they would be discriminated against because of their LGBTQ identity," the report states.

The Intersection of Race and LGBTQ Identity

The report also found LGBTQ people do not experience discrimination in a uniform manner. “There are really pronounced racial differences,” Casey explained. While the survey sample was not large enough to tease out specific differences in the experiences of African-American, Latinx and Asian-American respondents, the survey did allow researchers to compare the experiences of LGBTQ people of color and white LGBTQ people.

“LGBTQ people of color are at least twice as likely as white LGBTQ people say they have been personally discriminated against because they are LGBTQ when applying for jobs and when interacting with police, and six times more likely to say they have avoided calling the police (30 percent) due to concern for anti-LGBTQ discrimination, compared to white LGBTQ people (5 percent)," the report states.

feature Sexual harassment in the workplace: LGBTQ employees come forward

Casey said he was not surprised by these findings.

“Knowing what we know about the way multiple marginalized identities intersect ... seeing this racial disparity in the LGBTQ community was not surprising.” But, he added, “seeing them quantified in this way is very powerful.”

Generational Differences

While Casey said the survey did not uncover large age gaps in experiences of discrimination, he did note an important difference in the way younger and older generations think about the sources of discrimination.

Younger LGBTQ people (18-49 years of age) are more likely to say institutions (laws and government policies) are the source of discrimination, whereas older generations (50 and over) are more likely to identify individual prejudice as the problem, Casey explained.

Overall, Casey said the study helps “put some concrete data” to the experiences that LGBTQ people have been reporting for a long time.

“Even as we see advances like gay marriage or polling that says people are supportive of LGBTQ issues or know a gay person, average community members are saying that it doesn’t mean discrimination has gone away.”

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New study calculates climate change's economic bite will hit about $38 trillion a year by 2049

C limate change will reduce future global income by about 19% in the next 25 years compared to a fictional world that's not warming, with the poorest areas and those least responsible for heating the atmosphere taking the biggest monetary hit, a new study said.

Climate change's economic bite in how much people make is already locked in at about $38 trillion a year by 2049, according to Wednesday's study in the journal Nature by researchers at Germany's Potsdam Institute for Climate Impact Research. By 2100 the financial cost could hit twice what previous studies estimate.

“Our analysis shows that climate change will cause massive economic damages within the next 25 years in almost all countries around the world, also in highly-developed ones such as Germany and the U.S., with a projected median income reduction of 11% each and France with 13%,” said study co-author Leonie Wenz, a climate scientist and economist.

These damages are compared to a baseline of no climate change and are then applied against overall expected global growth in gross domestic product, said study lead author Max Kotz, a climate scientist. So while it's 19% globally less than it could have been with no climate change, in most places, income will still grow, just not as much because of warmer temperatures.

For the past dozen years, scientists and others have been focusing on extreme weather such as heat waves, floods, droughts, storms as the having the biggest climate impact. But when it comes to financial hit the researchers found “the overall impacts are still mainly driven by average warming, overall temperature increases,” Kotz said. It harms crops and hinders labor production, he said.

“Those temperature increases drive the most damages in the future because they're really the most unprecedented compared to what we've experienced historically,” Kotz said. Last year, a record-hot year, the global average temperature was 1.35 degrees Celsius (2.43 degrees Fahrenheit) warmer than pre-industrial times, according to the U.S. National Oceanic and Atmospheric Administration. The globe has not had a month cooler than 20th century average since February 1979.

In the United States, the southeastern and southwestern states get economically pinched more than the northern ones with parts of Arizona and New Mexico taking the biggest monetary hit, according to the study. In Europe, southern regions, including parts of Spain and Italy, get hit harder than places like Denmark or northern Germany.

Only Arctic adjacent areas — Canada, Russia, Norway, Finland and Sweden — benefit, Kotz said.

It also means countries which have historically produced fewer greenhouse gas emissions per person and are least able to financially adapt to warming weather are getting the biggest financial harms too, Kotz said.

The world's poorest countries will suffer 61% bigger income loss than the richest ones, the study calculated.

“It underlies some of the injustice elements of climate,” Kotz said.

This new study looked deeper than past research, examining 1,600 global areas that are smaller than countries, took several climate factors into account and examined how long climate economic shocks last, Kotz said. The study examined past economic impacts on average global domestic product per person and uses computer simulations to look into the future to come up with their detailed calculations.

The study shows that the economic harms over the next 25 years are locked in with emission cuts producing only small changes in the income reduction. But in the second half of this century that's when two different possible futures are simulated, showing that cutting carbon emissions now really pays off because of how the heat-trapping gases accumulate, Kotz said.

If the world could curb carbon pollution and get down to a trend that limits warming to 2 degrees Celsius (3.6 degrees Fahrenheit) above pre-industrial times, which is the upper limit of the 2015 Paris climate agreement, then the financial hit will stay around 20% in global income, Kotz said. But if emissions increase in a worst case scenario, the financial wallop will be closer to 60%, he said.

That shows that the public shouldn't think it's a financial “doomsday” and nothing can be done, Kotz said.

Still, it's worse than a 2015 study that predicted a worst case income hit of about 25% by the end of the century.

Marshall Burke, the Stanford University climate economist who wrote the 2015 study, said this new research's finding that the economic damage ahead is locked in and large “makes a lot of sense.”

Burke, who wasn't part of this study, said he has some issues with some of the technical calculations “so I wouldn't put a ton of weight on their specific numerical estimates, but I think the big picture is basically right.”

The conclusions are on the high end compared to other recent studies, but since climate change goes for a long time and economic damage from higher temperatures keep compounding, they “add up to very large numbers," said University of California Davis economist and environmental studies professor Frances Moore, who wasn't part of the study. That's why fighting climate change clearly passes economists' tests of costs versus benefits, she said.

Read more of AP’s climate coverage at http://www.apnews.com/climate-and-environment

Follow Seth Borenstein on X at @borenbears

The Associated Press’ climate and environmental coverage receives financial support from multiple private foundations. AP is solely responsible for all content. Find AP’s standards for working with philanthropies, a list of supporters and funded coverage areas at AP.org .

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Drinking 100% orange juice is linked to surprising health benefits, study finds

Pure orange juice drinkers consumed fewer calories than sugar-sweetened beverage drinkers, researchers said.

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Pure orange juice might have some unexpected benefits.

Researchers from Toronto Metropolitan University researched the effects of drinking 100% orange juice compared to a sugar-sweetened beverage (SSB), or "orange drink," on appetite, food intake and glycemic response in adults.

The study was funded by the Florida Department of Citrus . It was published in the journal Nutrients and also surveyed emotions and sensory characteristics associated with the beverage.

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Thirty-six "normal weight" adults were tasked with drinking either 100% orange juice, an orange drink or water before eating.

The researchers found that food and energy intake was lower in subjects who drank 100% orange juice compared to the orange drink.

"A little bit of orange seems to go a long way," study co-author Nick Bellissimo told Fox News Digital. (iStock)

Caloric compensation from 100% orange juice was 84%, while the orange drink was −25%. 

(Caloric compensation is the "regulation of energy intake by adjusting one's intake based on previous consumption," according to the National Institutes of Health.)

There was no significant difference in average appetite between the beverages, but blood glucose levels were lower after people drank the 100% orange juice .

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"Rest-of-day blood glucose concentrations were lower after 100% orange juice compared with the orange drink and water control," the study stated.

"In conclusion, consumption of 100% orange juice as a preload resulted in higher caloric compensation, lower total daily EI [energy intake], and lower blood glucose concentrations compared to the orange drink."

The researchers’ hypothesis was that the flavonoids in 100% orange juice slow down the digestion and absorption of sugar. (iStock)

Study co-author Nick Bellissimo, associate professor of nutritional physiology at Toronto Metropolitan University, reacted to the findings in a statement to Fox News Digital.

While a "number of dietary guidelines " recommend reducing sugar intake from "all sources," Bellissimo said, the findings suggested that 100% orange juice can be beneficial.

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"Orange juice is similar to a sugar-sweetened beverage in that it contains free sugars, but it also contains sucrose (fructose and glucose bound together), while also containing vitamin C and flavonoids," he noted.

The researchers’ hypothesis was that flavonoids in orange juice slow down the digestion and absorption of sugar.

"Thus, you are not seeing the same spike in blood glucose as you see with the SSB," Bellissimo said.

Study participants who consumed orange drinks ate more calories at lunch than the 100% orange juice drinkers. (iStock)

"Interestingly, the energy in the orange juice was compensated for at the next meal – i.e., participants decreased their food intake at lunch by an amount similar to the energy in the orange juice – whereas participants ate more calories at lunch after consuming the SSB."

Bellissimo confirmed that this effect on energy intake and glycemic response "persisted for the rest of the day." 

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"And participants consuming the orange juice actually consumed fewer calories, primarily by decreasing their carbohydrate intake," he said.

"A little bit of orange seems to go a long way," Bellissimo added.

People who drink 100% orange juice should mix it with some water for a more positive blood sugar result, a registered dietitian suggested. (iStock)

Ilana Muhlstein, a registered dietitian and nutritionist in Los Angeles, was not involved in the study but shared her thoughts on the study with Fox News Digital.

"The most important finding of the entire study is that the blood glucose concentrations were lower after 100% orange juice compared with an orange drink of the same calories, which shows that the body can recognize a difference between natural sugars and added sugars," she said.

As a dietitian, Muhlstein said she is "constantly encouraging people to drink water," especially prior to their meals, just as done in the study.

"The body can recognize a difference between natural sugars and added sugars."

"It’s important to note that drinking water has a meaningful impact on lowering blood sugar levels," she also pointed out. 

"If someone wanted to drink orange juice, I would encourage them to stick with 100% orange juice, versus an ‘orange drink’ sweetened with sugar, and do their best to mix it with some water for a more positive blood sugar result."

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Dr. Rosa Walsh, scientific research director at the Florida Department of Citrus, shared with Fox News Digital in a statement that although additional research is required to "further explore" the study results, the department is still "encouraged by these findings."

"It helps to reinforce the importance of choosing 100% fruit juice with no added sugar over sugar-sweetened beverages and shows the positive impact that incorporating a glass 100% orange juice into your daily diet may have on your overall health and wellness," Walsh said.

"An 8-ounce glass of 100% orange juice contains no added sugar and provides 100% of the recommended daily value of vitamin C and includes other essential vitamins and minerals."

For more Health articles, visit www.foxnews.com.com/health .

Angelica Stabile is a lifestyle writer for Fox News Digital.

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Doctor finds parallels between East Palestine symptoms, Gulf War illness

More than half of study participants reported brain fog, fatigue, and shortness of breath.

Two weeks after the train derailment in East Palestine, Dr. Beatrice Golomb remembers, federal and state officials were declaring the town safe. 

This took her aback.  

“We were a bit surprised by the messaging that seemed to say there wasn’t really a problem,” said Golomb, a University of California San Diego professor of medicine. “Absolutely if people were reporting health problems, there was a problem.” 

Golomb spent decades studying symptoms of Gulf War veterans exposed to toxic chemical burn pits. Last year, she began researching the symptoms of East Palestine residents, through a study funded by a three-year grant from the National Institutes of Health .  

The results are preliminary but striking.  

Sixty percent of participants reported concentration problems and brain fog. Another 60% reported shortness of breath. More than a third reported diarrhea, which Golomb noted was also the most common gastrointestinal symptom in Gulf War veterans.  

Golomb’s research doesn’t represent all East Palestine residents – just those who signed up for the study. Still, her expertise is invaluable for those who continue to experience symptoms and have few options for treatment, according to affected residents like Jami Wallace.

“She’s studied multiple chemical exposure before, and that’s exactly what we’re dealing with,” said Wallace, a former resident of East Palestine who relocated her family after the derailment. “We look at her as a ray of hope in the community.” 

To Wallace and many others, Golomb is “someone that can give us answers for both ourselves and our children.”  

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New symptoms, Gulf War illness similarities, emerge more than a year post-derailment

Golomb said a significant percentage of study participants meet criteria for what's known as "Gulf War illness.”  

“We are really seeing strong commonalities between the symptomatic profile reported in Gulf War veterans and what we’re seeing in East Palestine,” she said. 

The burn pits where Gulf War veterans were exposed to fumes from burning chemicals mirror the vent and burn of toxic chemicals in East Palestine that followed the derailment.  

More: Newly released videos of East Palestine derailment shows fireball, smoke in planned burn

State and local officials made the controversial decision to burn the chemicals in the tank cars to avoid what they thought would become a massive explosion. In the process, they exposed thousands of East Palestine residents to the chemicals through the air.  

More than a year later, residents are still experiencing the consequences every day, Wallace said. 

“We are seeing people become symptomatic that have never had symptoms before,” said Wallace. “Headaches, fatigue, muscle cramping.”  

Troubled by the symptoms she’s seeing among friends and family, Wallace now works with Golomb’s UC San Diego lab as community liaison to recruit residents to the study. 

“I think part of the issue is people think if they did not have symptoms, then they should not participate in the study,” said Wallace. “And in fact, we need everybody to participate.” 

Full study participation is critical to capturing effects of the chemical exposure that residents are experiencing now, as well as any that may surface in the future.   

Research requires building trust in East Palestine

In East Palestine, Golomb assumes the role of researcher, but also physician for residents seeking medical advice. She draws from her experience with treating veterans to do so. 

During an April question and answer session on the study for residents, Golomb recommended that residents limit their chemical exposure moving forward, even to those in household cleaning products and pesticides.  

The toxicity of these relatively mundane chemicals may be augmented by the residents’ chemical exposure from the derailment, according to Golomb, so she recommends using charcoal or vinegar instead. 

The role of serving as a support for the people of East Palestine is a critical part of the process, she said.

“This is a setting where people are only going to want to participate if they feel like you care about them and are trying to help them,” said Golomb. 

“In our work with Gulf War veterans, I think that population understands that we are their ally in their search for better health,” she said. “And they also are a population that had a lot of mistrust and a lot of cause for mistrust, because again, of early messaging denying that they were ill.” 

She hopes that her research will help the residents of East Palestine and surrounding areas affected by the derailment to get more resources. Gulf War veterans, for example, are eligible for disability compensation from the U.S. Department of Veterans Affairs.

“This is not their fault that the chemicals rained down on them,” Golomb said.  “A disaster befell the community, and they’re not getting the help and resources that they need.” 

For more information on Golomb's study, visit the Golomb Research Group’s website .