From Yale University: “Neuromarker for ADHD could improve diagnosis of the disorder”
11.23.22
Mallory Locklear
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Fred Mamoun
fred.mamoun@yale.edu
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Yale researchers identified differences in brain structure and activity in children with ADHD that could serve as a more objective diagnostic tool in the future.
Illustration by Michael S. Helfenbein.
For children with attention-deficit/hyperactivity disorder (ADHD), timely intervention is key. But diagnoses typically rely on questionnaires and observations of a child’s behavior, which are subjective and can lead to delays in treatment.
Yale researchers aim to establish a more objective measure of ADHD, and in a new study, they report an important step in that direction. Using brain imaging data from children with and without ADHD, they identified differences in brain structure and activity in children with ADHD that could serve as a neuromarker for the disorder.
They will present their findings Nov. 27 at the Radiological Society of North America annual meeting.
The subjectivity of ADHD assessments can cause children to be misdiagnosed or remain undiagnosed, explained Huang Lin, a research fellow at Yale School of Medicine and lead author of the study. Questionnaires given to a child’s parent or caregiver can be influenced by life events or stress, for example. The questionnaires also require caregivers to have spent a sufficient amount of time with the child, meaning children with less stable care may go undiagnosed. And as people age, they tend to show different symptoms, making diagnosis more difficult in older individuals.
“When people get older, the hyperactivity aspect of the disorder is decreased,” said Lin. “That can make it more difficult to diagnose observationally, and without a diagnosis, people with ADHD may assume that what they’re experiencing is standard.”
Lin and her colleagues used data from the Adolescent Brain Cognitive Development (ABCD) Study, which includes nearly 12,000 children from across the United States. The participants joined the study at age 9 or 10; researchers will continue tracking their biological and behavioral development into young adulthood, which will yield new data over the next few years. The demographics of the study participants mirror those of the U.S. population.
“That the study group is representative of the greater U.S. population means our findings will be generalizable to the U.S. population as well,” said Lin.
The researchers conducted a whole-brain analysis using images that measured brain structure and function in 7,805 9- to 10-year-olds. They found that the frontal cortex of the brain — an area responsible for functions like impulse control, attention, and working memory — was thinner in children with ADHD than in those without the disorder. Brain networks related to memory processing, alertness, and auditory processing were also different in children with ADHD. Further, white matter, which is composed of nerve fibers that project from one part of the brain to another, was thinner in children with ADHD. This could have implications for how different brain regions communicate with each other.
The pervasiveness of the differences was surprising, said Lin.
“I expected some brain regions to stand out. But we saw a more overall change throughout the entire brain,” she said.
The pattern the researchers uncovered was sufficiently stable across study participants that the research team used it to train a machine learning algorithm to predict who has ADHD based on brain images alone — meaning it holds promise as a diagnostic tool going forward, they said.
“The algorithm still needs further validation,” said Lin. “But once it is ready for clinical use, combining this more objective measure with the assessments already in use could allow more children to be accurately diagnosed in the future.”
The findings also emphasize that ADHD is not simply a disorder of behavior.
“Externalized behavior is certainly a part of ADHD, but there’s also a neurological correlate,” said Sam Payabvash, assistant professor of radiology and biomedical imaging at Yale School of Medicine and senior author of the study. “Better understanding of the neurological component will help with diagnosis and treatment in the future.”
It may also reduce the stigma attached to mental illness.
“If you measured someone’s blood pressure and found it was high, nobody would question that it was a condition that should be addressed. But a lot of people question diagnoses of mental illness,” said Lin. “Being able to measure it like we can blood pressure could help address that stigma.”
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Yale University is a private Ivy League research university in New Haven, Connecticut. Founded in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and one of the nine Colonial Colleges chartered before the American Revolution. The Collegiate School was renamed Yale College in 1718 to honor the school’s largest private benefactor for the first century of its existence, Elihu Yale. Yale University is consistently ranked as one of the top universities and is considered one of the most prestigious in the nation.
Chartered by Connecticut Colony, the Collegiate School was established in 1701 by clergy to educate Congregational ministers before moving to New Haven in 1716. Originally restricted to theology and sacred languages, the curriculum began to incorporate humanities and sciences by the time of the American Revolution. In the 19th century, the college expanded into graduate and professional instruction, awarding the first PhD in the United States in 1861 and organizing as a university in 1887. Yale’s faculty and student populations grew after 1890 with rapid expansion of the physical campus and scientific research.
Yale is organized into fourteen constituent schools: the original undergraduate college, the Yale Graduate School of Arts and Sciences and twelve professional schools. While the university is governed by the Yale Corporation, each school’s faculty oversees its curriculum and degree programs. In addition to a central campus in downtown New Haven, the university owns athletic facilities in western New Haven, a campus in West Haven, Connecticut, and forests and nature preserves throughout New England. As of June 2020, the university’s endowment was valued at $31.1 billion, the second largest of any educational institution. The Yale University Library, serving all constituent schools, holds more than 15 million volumes and is the third-largest academic library in the United States. Students compete in intercollegiate sports as the Yale Bulldogs in the NCAA Division I – Ivy League.
As of October 2020, 65 Nobel laureates, five Fields Medalists, four Abel Prize laureates, and three Turing award winners have been affiliated with Yale University. In addition, Yale has graduated many notable alumni, including five U.S. Presidents, 19 U.S. Supreme Court Justices, 31 living billionaires, and many heads of state. Hundreds of members of Congress and many U.S. diplomats, 78 MacArthur Fellows, 252 Rhodes Scholars, 123 Marshall Scholars, and nine Mitchell Scholars have been affiliated with the university.
Research
Yale is a member of the Association of American Universities (AAU) and is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation , Yale spent $990 million on research and development in 2018, ranking it 15th in the nation.
Yale’s faculty include 61 members of the National Academy of Sciences , 7 members of the National Academy of Engineering and 49 members of the American Academy of Arts and Sciences . The college is, after normalization for institution size, the tenth-largest baccalaureate source of doctoral degree recipients in the United States, and the largest such source within the Ivy League.
Yale’s English and Comparative Literature departments were part of the New Criticism movement. Of the New Critics, Robert Penn Warren, W.K. Wimsatt, and Cleanth Brooks were all Yale faculty. Later, the Yale Comparative literature department became a center of American deconstruction. Jacques Derrida, the father of deconstruction, taught at the Department of Comparative Literature from the late seventies to mid-1980s. Several other Yale faculty members were also associated with deconstruction, forming the so-called “Yale School”. These included Paul de Man who taught in the Departments of Comparative Literature and French, J. Hillis Miller, Geoffrey Hartman (both taught in the Departments of English and Comparative Literature), and Harold Bloom (English), whose theoretical position was always somewhat specific, and who ultimately took a very different path from the rest of this group. Yale’s history department has also originated important intellectual trends. Historians C. Vann Woodward and David Brion Davis are credited with beginning in the 1960s and 1970s an important stream of southern historians; likewise, David Montgomery, a labor historian, advised many of the current generation of labor historians in the country. Yale’s Music School and Department fostered the growth of Music Theory in the latter half of the 20th century. The Journal of Music Theory was founded there in 1957; Allen Forte and David Lewin were influential teachers and scholars.
In addition to eminent faculty members, Yale research relies heavily on the presence of roughly 1200 Postdocs from various national and international origin working in the multiple laboratories in the sciences, social sciences, humanities, and professional schools of the university. The university progressively recognized this working force with the recent creation of the Office for Postdoctoral Affairs and the Yale Postdoctoral Association.
Notable alumni
Over its history, Yale has produced many distinguished alumni in a variety of fields, ranging from the public to private sector. According to 2020 data, around 71% of undergraduates join the workforce, while the next largest majority of 16.6% go on to attend graduate or professional schools. Yale graduates have been recipients of 252 Rhodes Scholarships, 123 Marshall Scholarships, 67 Truman Scholarships, 21 Churchill Scholarships, and 9 Mitchell Scholarships. The university is also the second largest producer of Fulbright Scholars, with a total of 1,199 in its history and has produced 89 MacArthur Fellows. The U.S. Department of State Bureau of Educational and Cultural Affairs ranked Yale fifth among research institutions producing the most 2020–2021 Fulbright Scholars. Additionally, 31 living billionaires are Yale alumni.
At Yale, one of the most popular undergraduate majors among Juniors and Seniors is political science, with many students going on to serve careers in government and politics. Former presidents who attended Yale for undergrad include William Howard Taft, George H. W. Bush, and George W. Bush while former presidents Gerald Ford and Bill Clinton attended Yale Law School. Former vice-president and influential antebellum era politician John C. Calhoun also graduated from Yale. Former world leaders include Italian prime minister Mario Monti, Turkish prime minister Tansu Çiller, Mexican president Ernesto Zedillo, German president Karl Carstens, Philippine president José Paciano Laurel, Latvian president Valdis Zatlers, Taiwanese premier Jiang Yi-huah, and Malawian president Peter Mutharika, among others. Prominent royals who graduated are Crown Princess Victoria of Sweden, and Olympia Bonaparte, Princess Napoléon.
Yale alumni have had considerable presence in U.S. government in all three branches. On the U.S. Supreme Court, 19 justices have been Yale alumni, including current Associate Justices Sonia Sotomayor, Samuel Alito, Clarence Thomas, and Brett Kavanaugh. Numerous Yale alumni have been U.S. Senators, including current Senators Michael Bennet, Richard Blumenthal, Cory Booker, Sherrod Brown, Chris Coons, Amy Klobuchar, Ben Sasse, and Sheldon Whitehouse. Current and former cabinet members include Secretaries of State John Kerry, Hillary Clinton, Cyrus Vance, and Dean Acheson; U.S. Secretaries of the Treasury Oliver Wolcott, Robert Rubin, Nicholas F. Brady, Steven Mnuchin, and Janet Yellen; U.S. Attorneys General Nicholas Katzenbach, John Ashcroft, and Edward H. Levi; and many others. Peace Corps founder and American diplomat Sargent Shriver and public official and urban planner Robert Moses are Yale alumni.
Yale has produced numerous award-winning authors and influential writers, like Nobel Prize in Literature laureate Sinclair Lewis and Pulitzer Prize winners Stephen Vincent Benét, Thornton Wilder, Doug Wright, and David McCullough. Academy Award winning actors, actresses, and directors include Jodie Foster, Paul Newman, Meryl Streep, Elia Kazan, George Roy Hill, Lupita Nyong’o, Oliver Stone, and Frances McDormand. Alumni from Yale have also made notable contributions to both music and the arts. Leading American composer from the 20th century Charles Ives, Broadway composer Cole Porter, Grammy award winner David Lang, and award-winning jazz pianist and composer Vijay Iyer all hail from Yale. Hugo Boss Prize winner Matthew Barney, famed American sculptor Richard Serra, President Barack Obama presidential portrait painter Kehinde Wiley, MacArthur Fellow and contemporary artist Sarah Sze, Pulitzer Prize winning cartoonist Garry Trudeau, and National Medal of Arts photorealist painter Chuck Close all graduated from Yale. Additional alumni include architect and Presidential Medal of Freedom winner Maya Lin, Pritzker Prize winner Norman Foster, and Gateway Arch designer Eero Saarinen. Journalists and pundits include Dick Cavett, Chris Cuomo, Anderson Cooper, William F. Buckley, Jr., and Fareed Zakaria.
In business, Yale has had numerous alumni and former students go on to become founders of influential business, like William Boeing (Boeing, United Airlines), Briton Hadden and Henry Luce (Time Magazine), Stephen A. Schwarzman (Blackstone Group), Frederick W. Smith (FedEx), Juan Trippe (Pan Am), Harold Stanley (Morgan Stanley), Bing Gordon (Electronic Arts), and Ben Silbermann (Pinterest). Other business people from Yale include former chairman and CEO of Sears Holdings Edward Lampert, former Time Warner president Jeffrey Bewkes, former PepsiCo chairperson and CEO Indra Nooyi, sports agent Donald Dell, and investor/philanthropist Sir John Templeton,
Yale alumni distinguished in academia include literary critic and historian Henry Louis Gates, economists Irving Fischer, Mahbub ul Haq, and Nobel Prize laureate Paul Krugman; Nobel Prize in Physics laureates Ernest Lawrence and Murray Gell-Mann; Fields Medalist John G. Thompson; Human Genome Project leader and National Institutes of Health director Francis S. Collins; brain surgery pioneer Harvey Cushing; pioneering computer scientist Grace Hopper; influential mathematician and chemist Josiah Willard Gibbs; National Women’s Hall of Fame inductee and biochemist Florence B. Seibert; Turing Award recipient Ron Rivest; inventors Samuel F.B. Morse and Eli Whitney; Nobel Prize in Chemistry laureate John B. Goodenough; lexicographer Noah Webster; and theologians Jonathan Edwards and Reinhold Niebuhr.
In the sporting arena, Yale alumni include baseball players Ron Darling and Craig Breslow and baseball executives Theo Epstein and George Weiss; football players Calvin Hill, Gary Fenick, Amos Alonzo Stagg, and “the Father of American Football” Walter Camp; ice hockey players Chris Higgins and Olympian Helen Resor; Olympic figure skaters Sarah Hughes and Nathan Chen; nine-time U.S. Squash men’s champion Julian Illingworth; Olympic swimmer Don Schollander; Olympic rowers Josh West and Rusty Wailes; Olympic sailor Stuart McNay; Olympic runner Frank Shorter; and others.
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