Researchers have identified a consistent chemical difference in the brains of people with anxiety.
Anxiety has become one of the most visible mental health problems in the United States, showing up not only in clinics but also in schools, workplaces, and everyday family life. Although therapy and medication can help many people, anxiety disorders often go untreated, and even those who receive care do not always recover fully.
A new UC Davis Health study points to a possible biological clue: people with anxiety disorders appear to have lower levels of choline, an essential nutrient involved in brain function.
The study, published in the journal Molecular Psychiatry, reviewed 25 datasets from 24 published studies that used proton magnetic resonance spectroscopy (1H-MRS), a specialized MRI technique that measures brain chemistry. Together, the studies included 370 people with anxiety disorders and 342 people without anxiety. The analysis focused on generalized anxiety disorder, panic disorder, and social anxiety disorder.
The clearest finding was an 8% average reduction in choline-containing compounds in the brains of people with anxiety disorders. The difference was especially consistent in the prefrontal cortex, a region involved in planning, emotional control, decision making, and regulating behavior.
“This is the first meta-analysis to show a chemical pattern in the brain in anxiety disorders,” said Jason Smucny, co-author and assistant professor in the Department of Psychiatry and Behavioral Sciences. “It suggests nutritional approaches, like appropriate choline supplementation, may help restore brain chemistry and improve outcomes for patients.”
Why Choline Matters
Choline helps build cell membranes and supports brain processes involved in memory, mood regulation, and muscle control. It is also linked to acetylcholine, a chemical messenger important for learning and attention.
The body can make small amounts of choline, but most of it must come from food. Good dietary sources include eggs, salmon, meat, poultry, soybeans, and some cruciferous vegetables. Previous research has found that most people in the United States do not get the recommended amount.
The brain depends on a steady supply of choline. If anxiety keeps the brain in a prolonged state of alert, the researchers suggest it may raise the demand for choline-related compounds faster than the brain can replace them.
Anxiety May Strain the Brain’s Chemistry
Anxiety disorders are not simply “worrying too much.” They involve brain systems that detect danger, respond to stress, and decide whether a threat can be handled.
The amygdala helps signal fear and danger. The prefrontal cortex helps evaluate those signals and keep reactions in check. In anxiety disorders, that balance can break down. Everyday concerns may begin to feel urgent, threatening, or impossible to control.
The study also points to the role of norepinephrine, a chemical involved in the body’s fight-or-flight response. In people with anxiety disorders, this arousal system is often elevated. The researchers suggest that long-term activation of these stress systems may affect membrane metabolism, methylation reactions, and other choline-related processes in the brain.
Richard Maddock, senior author of the study, is a psychiatrist and research professor in the Department of Psychiatry and Behavioral Sciences. He is also a researcher at the UC Davis Imaging Research Center, which uses magnetic resonance imaging (MRI) to study brain health.
“Anxiety disorders are the most common mental illness in the United States, affecting about 30% of adults. They can be debilitating for people, and many people do not receive adequate treatment,” Maddock said.
Common anxiety disorders include generalized anxiety disorder, panic disorder, social anxiety disorder, and phobias.
A Window Into the Living Brain
The researchers used findings from 1H-MRS, a method that works inside an MRI scanner. Unlike standard MRI, which produces images of brain structure, 1H-MRS measures chemical signatures in brain tissue.
That allowed researchers to compare several neurometabolites, including choline, N-acetylaspartate, creatine, myo-inositol, glutamate, glutamine, GABA, and lactate. Choline stood out as the most consistent difference across anxiety disorders. The study also found signs of lower cortical N-acetylaspartate after excluding outlier datasets, which may suggest altered neuronal function, but the choline result was stronger.
Maddock had previously seen low choline levels in studies of people with panic disorder. Even so, the size and consistency of the new finding surprised him.
“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” Maddock said.
What This Does and Does Not Mean
The findings do not prove that low choline causes anxiety. They also do not show that supplements can treat anxiety disorders.
“We don’t know yet if increasing choline in the diet will help reduce anxiety. More research will be needed,” Maddock said.
He cautioned that people should not try to treat anxiety by taking large doses of choline supplements on their own. Too much supplementation can carry risks, and anxiety disorders should be evaluated and treated with medical guidance.
Still, the study raises an intriguing possibility: nutrition may influence the brain chemistry involved in anxiety, especially for people who are already falling short on key nutrients.
“Someone with an anxiety disorder might want to look at their diet and see whether they are getting the recommended daily amount of choline. Previous research has shown that most people in the U.S., including children, don’t get the recommended daily amount,” Maddock said. “Some forms of omega-3 fatty acids, like those found in salmon, may be especially good sources for supplying choline to the brain.”
Reference: “Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis” by Richard J. Maddock and Jason Smucny, 5 September 2025, Molecular Psychiatry.
DOI: 10.1038/s41380-025-03206-7
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