Summary: A large meta-analysis of 25 studies found that people with anxiety disorders have significantly lower levels of choline, a vital brain nutrient, compared to individuals without anxiety. This reduction was especially pronounced in the prefrontal cortex, which helps regulate emotion and behavior.
The findings point to a potential biological signature of anxiety disorders and raise the possibility that targeted nutritional strategies could help rebalance brain chemistry. Researchers emphasize that more work is needed to determine whether increasing choline intake can reduce anxiety symptoms.
Key Facts
- Lower Brain Choline: People with anxiety disorders showed an 8% reduction in choline, especially in the prefrontal cortex.
- Chemical Signature Identified: This is the first meta-analysis to uncover a consistent neurometabolic pattern in anxiety.
- Potential Nutritional Role: Results suggest dietary choline may influence brain chemistry, though clinical trials are needed.
Source: UC Davis
People with anxiety disorders have lower levels of choline in their brains, according to research from UC Davis Health.
The study, published in the Nature journal Molecular Psychiatry, analyzed data from 25 studies. The researchers compared the levels of neurometabolites — chemicals produced during brain metabolism — in 370 people with anxiety disorders to 342 people without anxiety.
They found the level of choline — an essential nutrient — was about 8% lower in those with anxiety disorders. The evidence for low choline was especially consistent in the prefrontal cortex, the part of the brain that helps control thinking, emotions 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 an 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) is vital for cell membranes and brain functions like memory, mood regulation and muscle control. The body makes a small amount, but most must come from food.
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 is also a researcher at the UC Davis Imaging Research Center, which uses magnetic resonance imaging (MRI) techniques to study brain health.
Maddock spent decades in clinical practice treating patients with anxiety disorders and conducting research on 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
Brain interactions affect anxiety
Anxiety disorders are linked to how different parts of the brain — like the amygdala, which influences our sense of safety or danger, and the prefrontal cortex, which is involved in planning and decision-making — respond to stress or potential threats.
Anxiety disorders are also linked to imbalances in neurotransmitters. For example, norepinephrine — part of the body’s “fight-or-flight” response — is often elevated in anxiety disorders.
Normally, the brain can tell the difference between potential threats that are manageable and those that are not. In anxiety disorders, manageable threats can seem overwhelming. For example, with generalized anxiety disorder, people worry excessively about everyday things and have trouble controlling their worries or feelings of nervousness.
Non-invasive technique identifies chemical levels in the brain
Maddock and Smucny have spent years studying brain chemistry and its association with mental illness using a non-invasive medical imaging technique known as proton magnetic resonance spectroscopy, or 1H-MRS.
The measurements are made using an MRI machine. 1H-MRS uses the magnetic fields and radio waves of an MRI to analyze the body. However, instead of creating an image of the body, it provides data about the chemicals that are present in the tissue.
Maddock had noticed low levels of choline in his earlier studies of patients with panic disorder. He decided to conduct a meta-analysis with Smucny. And even though they thought they would find low choline, he was still surprised by the results.
“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” Maddock said.
Most Americans don’t get enough choline
The researchers think the high fight-or-flight activity experienced in anxiety disorders may increase choline demand, lowering its levels.
“We don’t know yet if increasing choline in the diet will help reduce anxiety. More research will be needed,” Maddock said. He cautions that people with anxiety should not self-medicate with excessive choline supplements.
But he notes a healthy diet is essential for all aspects of health, 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 rich in choline include beef liver, eggs (particularly the yolk), beef, chicken, fish, soybeans and milk, among others.
Key Questions Answered:
A: People with anxiety disorders had about 8% lower choline levels in their brains.
A: In the prefrontal cortex, a region involved in thinking, emotions, and behavior.
A: Not without medical guidance; more research is needed to determine if supplementation reduces anxiety.
About this anxiety research news
Author: Lisa Howard
Source: UC Davis
Contact: Lisa Howard – UC Davis
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis” by Jason Smucny et al. Molecular Psychiatry
Abstract
Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis
Background
Anxiety disorders (AnxDs) are highly prevalent and often untreated or unresponsive to treatment. Although proton magnetic resonance spectroscopy (1H-MRS) studies of AnxDs have been conducted for over 25 years, a consensus regarding neurometabolic abnormalities in these conditions is lacking.
Methods
A systematic review and meta-analysis of 1H-MRS studies of AnxDs (social anxiety disorder, generalized anxiety disorder, and panic disorder) identified 25 published datasets meeting inclusion criteria. These compared neurometabolites between 370 patients and 342 controls, including n-acetlyaspartate (NAA), total creatine, total choline (tCho), myo-inositol, glutamate, glutamate+glutamine, GABA, and lactate.
Results
Across AnxDs, tCho was significantly reduced in prefrontal cortex and across all cortical regions. Effect sizes for cortical tCho were significantly more negative in studies with better measurement quality, with Hedges’ g = −0.64 and an 8% mean reduction. NAA was unchanged in prefrontal cortex but reduced across all cortical regions (after exclusions). These abnormalities did not differ between the three disorders. No other neurometabolites differed significantly.
Discussion
Reduced choline-containing compounds in cortical regions is a consistent, transdiagnostic abnormality in AnxDs. Notably, arousal-related neuromodulators, including norepinephrine, alter membrane phospholipid homeostasis and methylation reactions, which influence brain tCho levels. This suggests that chronically elevated arousal in AnxDs may increase neurometabolic demand for choline compounds without a proportionate increase in brain uptake, leading to reduced tCho levels.
Reduced cortical NAA suggests compromised neuronal function in AnxDs. Future studies may clarify the clinical significance of reduced cortical tCho and the possibility that appropriate choline supplementation could have therapeutic benefit in anxiety disorders.
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