Millions With Anxiety Share One Striking Brain Chemistry Difference

Researchers analyzing data from 25 studies have found that people with anxiety disorders consistently show lower levels of choline, an essential nutrient involved in brain signaling and emotional regulation.

Research from UC Davis Health shows that people with anxiety disorders have noticeably lower amounts of choline in their brains. Choline is an essential nutrient involved in brain metabolism and communication.

The findings, published in the Nature journal Molecular Psychiatry, come from an analysis of 25 studies. The team compared neurometabolite levels, which are chemicals created during brain metabolism, in 370 people diagnosed with anxiety disorders and 342 people without anxiety.

Across these studies, choline levels were about 8% lower in individuals with anxiety disorders. This difference was most clearly seen in the prefrontal cortex, the area of the brain responsible for guiding thought processes, emotional control, and 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.”

Choline (pronounced KOE lean) plays a key role in maintaining cell membranes and supporting memory, mood, and muscle movement. The body produces only a small amount, so most must come from dietary sources.

Anxiety Disorders Are Widespread and Often Untreated

Anxiety disorders affect about 30% of adults.

Richard Maddock, senior author of the study, is a psychiatrist and research professor in the Department of Psychiatry and Behavioral Sciences. He also conducts research at the UC Davis Imaging Research Center, where MRI technology is used to explore brain health.

Maddock has spent many years treating patients with anxiety disorders and investigating the biological factors that contribute to these conditions.

“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.

Anxiety disorders include:

• Generalized anxiety disorder
• Panic disorder
• Social anxiety disorders
• Phobias

How Brain Circuits and Chemicals Shape Anxiety Responses

Anxiety disorders involve changes in how different brain regions respond to stress. The amygdala, which influences feelings of safety or danger, and the prefrontal cortex, which helps with planning and decision-making, often react differently in people with anxiety disorders.

Chemical imbalances also play a role. For example, the neurotransmitter norepinephrine, a key part of the body’s “fight-or-flight” response, is frequently elevated in anxiety disorders.

Under typical circumstances, the brain can distinguish between manageable challenges and true threats. In anxiety disorders, everyday situations may feel far more dangerous. People with generalized anxiety disorder, for instance, often experience persistent worry about routine concerns and struggle to control feelings of nervousness.

MRI-Based Technique Reveals Brain Chemical Differences

Maddock and Smucny have long studied brain chemistry and its connection to mental illness using a non-invasive method called proton magnetic resonance spectroscopy, or 1H-MRS.

This technique relies on an MRI machine to measure chemicals inside tissues. Instead of creating an image of the body, 1H-MRS identifies the specific metabolites present in the brain.

In earlier work, Maddock noticed that patients with panic disorder showed reduced choline levels. That observation helped motivate the current meta-analysis. Despite expecting to see lower choline, Maddock was surprised by the strength of the pattern.

“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” Maddock said.

Dietary Choline Intake May Be Important for Brain Health

The researchers suspect that the heightened fight-or-flight activity seen in anxiety disorders may increase the brain’s need for choline, leading to lower levels.

“We don’t know yet if increasing choline in the diet will help reduce anxiety. More research will be needed,” Maddock said. He warned that people should not attempt to self-treat anxiety using large amounts of choline supplements.

He emphasized the importance of good nutrition for overall well-being, including mental health.

“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.”

Other foods that provide choline include beef liver, eggs (particularly the yolk), beef, chicken, fish, soybeans, and milk, among others.

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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