Gerald Maguire has stuttered since childhood, but you might not guess it from talking to him. For the past 25 years, Maguire a psychiatrist at the University of California, Riverside has been treating his disorder with antipsychotic medications not officially approved for the condition. Only with careful attention might you discern his occasional stumble on multisyllabic words like statistically and pharmaceutical.
Maguire has plenty of company: More than 70 million people worldwide, including about 3 million Americans, stutter that is, they have difficulty with the starting and timing of speech, resulting in halting and repetition. That number includes approximately 5 percent of children, many of whom outgrow the condition, and 1 percent of adults. Their numbers includepresidential candidate Joe Biden,deep-voiced actor James Earl Jonesand actressEmily Blunt. Though those people and many others, including Maguire, have achieved career success, stuttering can contribute to social anxiety and draw ridicule or discrimination by others.
Maguire has been treating people who stutter, and researching potential treatments, for decades. He receives daily emails from people who want to try medications, join his trials, or even donate their brains to his university when they die. Hes now embarking on a clinical trial of a new medication, called ecopipam, that streamlined speech and improved quality of life in a small pilot study in 2019.
Others, meanwhile, are delving into the root causes of stuttering, which also may point to novel treatments. In past decades, therapists mistakenly attributed stuttering to defects of the tongue and voice box, to anxiety, trauma or even poor parenting and some still do. Yet others have long suspected that neurological problems might underlie stuttering, says J. Scott Yaruss, a speech-language pathologist at Michigan State University in East Lansing. The first data to back up that hunch came in 1991, Yaruss says, when researchers reportedaltered blood flow in the brains of people who stuttered. Over the past two decades, continuing research has made it more apparent that stuttering is all in the brain.
We are in the middle of an absolute explosion of knowledge being developed about stuttering, Yaruss says.
Theres still a lot to figure out, though. Neuroscientists have observed subtle differences in the brains of people who stutter, but they cant be certain if those differences are the cause or a result of the stutter. Geneticists are identifying variations in certain genes that predispose a person to stutter, but the genes themselves are puzzling: Only recently have their links to brain anatomy become apparent.
Maguire, meanwhile, is pursuing treatments based on dopamine, a chemical messenger in the brain that helps to regulate emotions and movement (precise muscle movements, of course, are needed for intelligible speech). Scientists are just beginning to braid these disparate threads together, even as they forge ahead with early testing for treatments based on their discoveries.
Looking at a standard brain scan of someone who stutters, a radiologist wont notice anything amiss. Its only when experts look closely, with specialized technology that shows the brains in-depth structure and activity during speech, that subtle differences between groups who do and dont stutter become apparent.
The problem isnt confined to one part of the brain. Rather, its all about connections between different parts, says speech-language pathologist and neuroscientist Soo-Eun Chang of the University of Michigan in Ann Arbor. For example, in the brains left hemisphere, people who stutter often appear to have slightly weaker connections between the areas responsible for hearing and for the movements that generate speech. Chang has also observed structural differences in the corpus callosum, the big bundle of nerve fibers that links the left and right hemispheres of the brain.
These findings hint that stuttering might result from slight delays in communication between parts of the brain. Speech, Chang suggests, would be particularly susceptible to such delays because it must be coordinated at lightning speed.
Chang has been trying to understand why about 80 percent of kids who stutter grow up to have normal speech patterns, while the other 20 percent continue to stutter into adulthood. Stuttering typically begins when children first start stringing words together into simple sentences, around age 2. Chang studies children for up to four years, starting as early as possible, looking for changing patterns in brain scans.
Its no easy feat to convince such young children to hold still in a giant, thumping, brain-imaging machine. The team has embellished the scanner with decorations that hide all the scary parts. (It looks like an ocean adventure, Chang says.) In kids who lose their stutter, Changs team has observed that the connections between areas involved in hearing and ones involved in speech movements get stronger over time. Butthat doesnt happen in children who continue to stutter.
In another study, Changs group looked at how the different parts of the brain work simultaneously, or dont, using blood flow as a proxy for activity. They found a link between stuttering and a brain circuit called the default mode network, which has roles in ruminating over ones past or future activities, as well as daydreaming. In children who stutter, the default mode network seems to insert itself like a third person butting in on a romantic date intothe conversation between networks responsible for focusing attention and creating movements. That could also slow speech production, she says.
These changes to brain development or structure might be rooted in a persons genes, but an understanding of this part of the problem has also taken time to mature.
In early 2001, geneticist Dennis Drayna received a surprising email: I am from Cameroon, West Africa. My father was a chief. He had three wives and I have 21 full and half siblings. Almost all of us stutter, Drayna recalls it saying. Do you suppose there could be something genetic in my family?
Drayna, who worked at the National Institute on Deafness and Other Communication Disorders, already had a longstanding interest in the inheritance of stuttering. His uncle and elder brother stuttered, and his twin sons did so as children. But he was reluctant to make a transatlantic journey based on an email, and wary that his clinical skills werent up to analyzing the familys symptoms. He mentioned the email to current National Institutes of Health director Francis Collins (director of the National Human Genome Research Institute at that time), who encouraged him to check it out, so he booked a ticket to Africa. He has also traveled to Pakistan, where intermarriage of cousins can reveal gene variants linked to genetic disorders in their children.
Even with those families, finding the genes was slow going: Stuttering isnt inherited in simple patterns like blood types or freckles are. But eventually, Draynas team identified mutations in four genes GNPTAB,GNPTGandNAGPAfrom the Pakistan studies, andAP4E1from the clan in Cameroonthat he estimates may underlie as many as one in five cases of stuttering.
Oddly, none of the genes that Drayna identified have an obvious connection to speech. Rather, they all are involved in sending cellular materials to the waste-recycling compartment called thelysosome. It took more work before Draynas team linked the genes to brain activity.
They started by engineering mice to have one of the mutations theyd observed in people, in the mouse version ofGNPTAB, to see if it affected the mices vocalizations.Mice can be quite chatty, but much of their conversation takes place in an ultrasonic range that people cant hear. Recording the ultrasonic calls of pups, the team observed patterns similar to human stuttering. They have all these gaps and pauses in their train of vocalizations, says Drayna, who cowrote an overview ofgenetics research on speech and language disordersfor theAnnual Review of Genomics and Human Genetics.
Still, the team struggled to spot any clear defect in the animals brains until one determined researcher found that there were fewer of the cells called astrocytes in the corpus callosum. Astrocytesdo big jobs that are essential for nerve activity: providing the nerves with fuel, for example, and collecting wastes. Perhaps, Drayna muses, the limited astrocyte population slows down communication between the brain hemispheres by a tiny bit, only noticeable in speech.
Draynas research has received mixed reviews. Its really been the pioneering work in the field, says Angela Morgan, a speech-language pathologist at the University of Melbourne and Murdoch Childrens Research Institute in Australia. On the other hand, Maguire has long doubted that mutations in such important genes, used in nearly all cells, could cause defects only in the corpus callosum, and only in speech. He also finds it difficult to compare mouse squeaks to human speech. Thats a bit of a stretch, he says.
Scientists are sure there are more stuttering genes to find. Drayna has retired, but Morgan and collaborators areinitiating a large-scale studyin the hopes of identifying additional genetic contributors in more than 10,000 people.
Maguire has been tackling stuttering from a very different angle: investigating the role of dopamine, a key signaling molecule in the brain. Dopamine can ramp up or down the activity of neurons, depending on the brain location and the nerve receptors it sticks to. There are five different dopamine receptors (named D1, D2, and so on) that pick up the signal and respond.
During the 1990s, Maguire and colleagues were among the first to use a certain kind of brain scan, positron emission tomography, on people who stutter. They foundtoomuch dopamine activityin these peoples brains. That extra dopamine seems to stifle the activity of some of the brain regions that Chang and others have linked to stuttering.
Backing up the dopamine connection, other researchers reported in 2009 that people with a certainversion of the D2 receptor gene, one that indirectly enhances dopamine activity, are more likely to stutter.
So Maguire wondered: Could blocking dopamine be the answer? Conveniently, antipsychotic drugs do just that. Over the years, Maguire has conducted small, successful clinical studies with these medications includingrisperidone,olanzapineandlurasidone. (Personally, he prefers the last because it doesnt cause as much weight gain as the others.) The result: Your stuttering wont completely go away, but we can treat it, he says.
None of those medications are approved for stuttering by the US Food and Drug Administration, and they can cause unpleasant side effects, not just weight gain but also muscle stiffness and impaired movement. In part, thats because they act on the D2 version of the dopamine receptor. Maguires new medication, ecopipam, works on the D1 version, which he expects will diminish some side effects though hell have to watch for others, such as weight loss and depression.
In a small study of 10 volunteers, Maguire, Yaruss and colleagues found that people who took ecopipamstuttered lessthan they did pre-treatment. Quality-of-life scores, related to feelings such as helplessness or acceptance of their stutter, also improved for some participants.
Ecopipam isnt the only treatment under consideration. Back in Michigan, Chang hopes thatstimulation of specific parts of the brain during speech could improve fluency. The team uses electrodes on the scalp to gently stimulate a segment of the hearing area, aiming to strengthen connections between that spot and the one that manages speech movements. (This causes a brief tickle sensation before fading, Chang says.) The researchers stimulate the brain while the person undergoes traditional speech therapy, hoping to enhance the therapys effects. Because of the Covid-19 pandemic, the team had to stop the study with 24 subjects out of a planned 50. Theyre analyzing the data now.
Dopamine, cellular waste disposal, neural connectivity how do they fit together? Chang notes that one of the brains circuits involved in stuttering includes two areas that make and use dopamine, which might help explain why dopamine is important in the disorder.
She hopes that neuroimaging can unite the different ideas. As a first stab, she and collaborators compared the problem areas identified by her brain scans tomaps of where various genes are active in the brain. Two of Draynas genes,GNPTGandNAGPA, were active at high levels in the speech and hearing network in the brains of non-stutterers, she saw. That suggests those genes are really needed in those areas, bolstering Draynas hypothesis that defects in the genes would interfere with speech.
The team also observed something novel: Genes involved in energy processing were active in the speech and hearing areas. Theres a big rise in brain activity during the preschool years, when stuttering tends to start, Chang says. Perhaps, she theorizes, those speech-processing regions dont get all the energy they need at a time when they really need to be cranking at maximum power. With that in mind, she plans to look for mutations in those energy-control genes in children who stutter. There are obviously a lot of dots that need to be connected, she says.
Maguire is also connecting dots: He says hes working on a theory to unite his work with Draynas genetic findings. Meanwhile, after struggling through med school interviews and choosing a career in talk therapy despite his difficulties with speech, hes hopeful about ecopipam: With colleagues, hes starting a new study that willcompare 34 people on ecopipam with 34 on placebo. If that treatment ever becomes part of the standard stuttering tool kit, he will have realized a lifelong dream.
Amber Dance is an award-winningfreelance science journalist based in Southern California. She contributes to publications includingPNAS Front Matter,The Scientist, andNature. Find Amber on Twitter @amberldance
A version of this article was originally published at Knowable Magazine and has been republished here with permission. Knowable can be found on Twitter @KnowableMag. Sign up for their newsletter here.
Read more here:
'It's all in the brain': The science behind stuttering - Genetic Literacy Project
- Feline Genetics And Why Orange Cats Are The Most Special - Hackaday - June 10th, 2025 [June 10th, 2025]
- Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma - Nature - June 10th, 2025 [June 10th, 2025]
- New genetics will transform the South African nut industry - Fruitnet - June 10th, 2025 [June 10th, 2025]
- Missouri farmer: crop genetics offset weather - Brownfield Ag News - June 1st, 2025 [June 1st, 2025]
- Human Genetics Laboratory increasing automation to meet growing demand for testing - University of Nebraska Medical Center - June 1st, 2025 [June 1st, 2025]
- Myriad Genetics Highlights New Research Advancements and Oncology Innovations at 2025 ASCO Annual Meeting - Yahoo Finance - June 1st, 2025 [June 1st, 2025]
- Unlocking the genetics of blindness: New hope for sufferers of inherited retinal diseases - Medical Xpress - June 1st, 2025 [June 1st, 2025]
- Spotting Winners: Myriad Genetics (NASDAQ:MYGN) And Therapeutics Stocks In Q1 - Yahoo Finance - June 1st, 2025 [June 1st, 2025]
- Myriad Genetics, Inc. (MYGN) Showcases Breakthrough MRD Data and AI-Driven Cancer Tools at ASCO 2025 - Yahoo Finance - June 1st, 2025 [June 1st, 2025]
- Doubling down on genetics-guided drug development, Regeneron to buy 23andMe - FirstWord Pharma - May 21st, 2025 [May 21st, 2025]
- Research team homes in on genetics behind blackberry thorns - Phys.org - May 21st, 2025 [May 21st, 2025]
- Trade mission to Mexico aims to expand reach of US beef cattle genetics - Brownfield Ag News - May 21st, 2025 [May 21st, 2025]
- A Life Transformed by Genetics: Woman With Coral Springs Roots Uses BRCA Positive Status to Educate, Empower Others - TAPinto - May 21st, 2025 [May 21st, 2025]
- Regeneron in $256M deal to acquire human genetics and bio company - Westfair Communications - May 21st, 2025 [May 21st, 2025]
- Insights in Cannabis Genetics with Anna Schwabe, PhD - Cannabis Science and Technology - May 12th, 2025 [May 12th, 2025]
- Role of Genetics in Maturity-Onset Diabetes of the Young and Personalized Diabetes Care , explores review - Medical Dialogues - May 12th, 2025 [May 12th, 2025]
- The Sophia Case: When Parenthood Isnt Just About Genetics - The Times of Israel - May 12th, 2025 [May 12th, 2025]
- Commentary: This genetics firm didn't resurrect the extinct dire wolf, but did achieve a breakthrough in hype - Los Angeles Times - April 27th, 2025 [April 27th, 2025]
- WHAT THE TECH? How the sale of genetics testing company could impact you - Local 3 News - April 27th, 2025 [April 27th, 2025]
- Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes - Nature - April 27th, 2025 [April 27th, 2025]
- Daily briefing: Potato pangenome reveals the complex genetics of the humble spud - Nature - April 27th, 2025 [April 27th, 2025]
- Chinese and other global scientists jointly solve genetics mystery of Mendel's peas - China Daily - April 27th, 2025 [April 27th, 2025]
- Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease - Nature - April 19th, 2025 [April 19th, 2025]
- Zevra Announces Publication of MIPLYFFA Mechanism of Action Manuscript in Molecular Genetics and Metabolism - Yahoo Finance - April 19th, 2025 [April 19th, 2025]
- Myriad Genetics price target lowered to $9 from $11 at BofA - Yahoo Finance - April 19th, 2025 [April 19th, 2025]
- Genetics of hemophilia: Why mutations matter more than ever in diagnosis and treatment - Firstpost - April 19th, 2025 [April 19th, 2025]
- RFK Jr. sparks backlash with autism comments, dismissing genetics and calling disorder preventable - 13newsnow.com - April 19th, 2025 [April 19th, 2025]
- The Crucial Role Of Genetics In Rare Diseases - BW Healthcare World - April 19th, 2025 [April 19th, 2025]
- How AI and genetics are revolutionizing psychiatric diagnosis and treatment [PODCAST] - KevinMD.com - April 10th, 2025 [April 10th, 2025]
- Opus Genetics Announces One-Month Clinical Data from Pediatric Patient in Phase 1/2 Trial of OPGx-LCA5 Gene Therapy in Inherited Retinal Diseases -... - April 10th, 2025 [April 10th, 2025]
- A genetics company just revived the dire wolf, sort of - Boy Genius Report - April 10th, 2025 [April 10th, 2025]
- Slammed 25% Opus Genetics, Inc. (NASDAQ:IRD) Screens Well Here But There Might Be A Catch - simplywall.st - April 10th, 2025 [April 10th, 2025]
- Do genetics hold the key to the US' European green crab problem? - Oceanographic Magazine - April 10th, 2025 [April 10th, 2025]
- Sequence errors are canaries in a coal mine in genetics studies, sleuth says - Retraction Watch - March 30th, 2025 [March 30th, 2025]
- Significance of noninvasive prenatal testing using massively parallel sequencing in women with twin or vanishing twin pregnancies | Journal of Human... - March 30th, 2025 [March 30th, 2025]
- All You Need to Know About Atossa Genetics (ATOS) Rating Upgrade to Buy - Yahoo Finance - March 30th, 2025 [March 30th, 2025]
- 23andMe Stock Is Surging After a Bankruptcy Judge Cleared Genetics Business Sale. Heres Why You Need to Stay Far Away From ME Shares. - Barchart - March 30th, 2025 [March 30th, 2025]
- Dairy producers leverage genetics to optimize milk composition for processing - Feedstuffs - March 30th, 2025 [March 30th, 2025]
- Several Insiders Invested In Opus Genetics Flagging Positive News - Yahoo Finance - March 30th, 2025 [March 30th, 2025]
- Human genetics and biotechnology company 23andMe to pursue bankruptcy sale after failed prepetition attempt Case Profile - ION Analytics - March 30th, 2025 [March 30th, 2025]
- AP Biology Students At NLHS Explore Genetics With Build-A-Baby Monster Lab - EastTexasRadio.com - March 30th, 2025 [March 30th, 2025]
- Winners And Losers Of Q4: Myriad Genetics (NASDAQ:MYGN) Vs The Rest Of The Therapeutics Stocks - Yahoo Finance - March 15th, 2025 [March 15th, 2025]
- Helix Unveils Groundbreaking Real-World Insights at the ACMG Annual Clinical Genetics Meeting, Driving Clinical Care Forward - PR Newswire - March 15th, 2025 [March 15th, 2025]
- S2 Episode 3: Molecular Classification and Genetics of Endometrial Cancer - Medscape - March 15th, 2025 [March 15th, 2025]
- Fowl Play: How Chicken Genetics Barons Created the Egg Crisis - The Big Newsletter - March 15th, 2025 [March 15th, 2025]
- Exposure to violence alters human genetics for future generations - Earth.com - March 5th, 2025 [March 5th, 2025]
- Family-based genetics identifies association of CUBN IL1RL1 and PRKN variants with leprosy in Bangladesh - Nature.com - March 5th, 2025 [March 5th, 2025]
- The role of genetics in infant hearing loss: What parents need to know - The Times of India - March 5th, 2025 [March 5th, 2025]
- Analyzing Genetics May Lead to Better Contraceptive Experiences for Women - Yale School of Medicine - March 5th, 2025 [March 5th, 2025]
- Fulgent Genetics Full Year 2024 Earnings: EPS Beats Expectations - Yahoo Finance - March 5th, 2025 [March 5th, 2025]
- Myriad Genetics Reports Fourth Quarter and Full-Year 2024 Financial Results; Full-year 2024 revenue of $838 million grew 11% year-over-year, the... - February 25th, 2025 [February 25th, 2025]
- Dual recombinase-mediated intersectional genetics defines the functional heterogeneity of neural stem cells in adult hippocampus - Nature.com - February 25th, 2025 [February 25th, 2025]
- Myriad Genetics Partners with PATHOMIQ to add Artificial Intelligence Technology Platform to its Oncology Portfolio - Yahoo Finance - February 25th, 2025 [February 25th, 2025]
- The Genetics of Creativity: Can Creative Talent Be Inherited? - Etownian - February 25th, 2025 [February 25th, 2025]
- Weight and metabolism determined more by genetics than diet - WVTF - February 25th, 2025 [February 25th, 2025]
- Beyond genetics: The biggest factors that influence health and aging - Earth.com - February 25th, 2025 [February 25th, 2025]
- Study finds lifestyle, environment have greater impact on lifespan than genetics - CBS Boston - February 25th, 2025 [February 25th, 2025]
- 6 Things to Know About Genetics in GI Cancers - Gastroenterology & Endoscopy News - February 25th, 2025 [February 25th, 2025]
- Virologist Wendy Barclay: Wild avian viruses are mixing up their genetics all the time. Its like viral sex on steroids - The Guardian - February 3rd, 2025 [February 3rd, 2025]
- Do you find coffee too bitter? Scientists explain how your genetics and roasting process affect the flavour - Hindustan Times - February 3rd, 2025 [February 3rd, 2025]
- 2025 Illinois Performance Tested Bull Sale prioritizes trusted genetics for herd growth - Morning Ag Clips - - February 3rd, 2025 [February 3rd, 2025]
- Game-Changing Cancer Detection Tool Spots What Others Miss: New Breakthrough from SOPHiA GENETICS - StockTitan - February 3rd, 2025 [February 3rd, 2025]
- Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS -... - January 23rd, 2025 [January 23rd, 2025]
- deCODE genetics: Complete recombination map of the human-genome, a major step in genetics - Financial Times - January 23rd, 2025 [January 23rd, 2025]
- Myriad Genetics Announces Hereditary Cancer Risk Assessment Program Study Published in Obstetrics & Gynecology - Yahoo Finance - January 23rd, 2025 [January 23rd, 2025]
- Bjarni V. Halldorsson and Kari Stefansson, scientists at deCODE genetics, discuss the paper: Complete recombination map of the human-genome, published... - January 23rd, 2025 [January 23rd, 2025]
- Myriad Genetics Doubles Cancer Testing Rates with Revolutionary Online Screening Tool - StockTitan - January 23rd, 2025 [January 23rd, 2025]
- Genetics, brain development, and mental health shape teen eating - News-Medical.Net - January 15th, 2025 [January 15th, 2025]
- Building Better Flu Shots Based on Antibody Responses and Genetics - Vax-Before-Travel - January 15th, 2025 [January 15th, 2025]
- Its in the Genes: Weight and Metabolism Determined by Genetics More Than Diet - Cville Right Now - January 15th, 2025 [January 15th, 2025]
- It's in the genes: Weight and metabolism determined by genetics more than diet - Medical Xpress - January 15th, 2025 [January 15th, 2025]
- Trump and Musk are obsessed with genetics but theres no science behind their simplistic views - The Guardian - January 1st, 2025 [January 1st, 2025]
- From Stonehenge's origins to ice age baby genetics how well did you follow this year's top archaeology stories? - Livescience.com - January 1st, 2025 [January 1st, 2025]
- William Thilly, MIT genetics professor who invented Apple Jacks cereal, dies at 79 - The Boston Globe - January 1st, 2025 [January 1st, 2025]
- Is Atossa Genetics (ATOS) Stock Outpacing Its Medical Peers This Year? - Yahoo Finance - December 23rd, 2024 [December 23rd, 2024]
- With 54% ownership, Fulgent Genetics, Inc. (NASDAQ:FLGT) boasts of strong institutional backing - Yahoo Finance - December 23rd, 2024 [December 23rd, 2024]
- Using the PERC Database to Gather Insights on Epilepsy Genetics: Julie Ziobro, MD, PhD; John Schreiber, MD - Neurology Live - December 23rd, 2024 [December 23rd, 2024]
- Myriad Genetics' Breakthrough Cancer Test Named Top 10 Genomic Advance by Leading Journal - StockTitan - December 23rd, 2024 [December 23rd, 2024]
- Redecan Cannabis Launches New Limited-Edition Genetics and Expands Signature 'Wrapped & Redee' Pre-roll Line for the Holidays - Yahoo Finance - December 23rd, 2024 [December 23rd, 2024]
- Surprising yields, impressive genetics and an early harvest in 2024 Ohio Ag Net - Ohio's Country Journal and Ohio Ag Net - December 9th, 2024 [December 9th, 2024]