Summary: A comprehensive meta-analysis of 25 studies shows that people with anxiety disorders have noticeably lower levels of choline—a vital brain nutrient—than individuals without anxiety. The reduction was most consistent in the prefrontal cortex, a brain region involved in emotion regulation and decision-making.
These findings point to a possible biological signature of anxiety disorders and raise the question of whether targeted dietary or supplemental strategies might help restore neurometabolic balance. Researchers stress that clinical trials are needed to determine whether increasing choline intake reduces anxiety symptoms.
Key Facts
- Lower brain choline: People with anxiety disorders showed about an 8% reduction in choline, with the effect strongest in the prefrontal cortex.
- Consistent chemical pattern: This is the first meta-analysis to reveal a reproducible neurometabolic pattern across anxiety disorders.
- Potential nutritional implications: Findings suggest dietary choline could influence brain chemistry, but clinical evidence for supplementation is not yet established.
Source: UC Davis
People with anxiety disorders have lower brain choline, according to a UC Davis Health analysis.
Published in the journal Molecular Psychiatry, the study pooled data from 25 published datasets. The investigators compared neurometabolite measures from proton magnetic resonance spectroscopy (1H-MRS) in 370 people diagnosed with anxiety disorders and 342 control participants without anxiety.
Across studies, total choline (tCho)—a marker of choline-containing compounds important for cell membranes and brain signaling—was on average about 8% lower in participants with anxiety disorders. The most consistent deficits appeared in the prefrontal cortex, an area central to thinking, emotional control and behavior.
“This meta-analysis is the first to demonstrate a transdiagnostic chemical pattern in the brains of people with anxiety disorders,” said Jason Smucny, co-author and assistant professor in the Department of Psychiatry and Behavioral Sciences at UC Davis. “The result suggests that nutritional approaches, such as carefully dosed choline supplementation, might help rebalance brain chemistry, but further research is required.”
Choline (pronounced KOE-leen) supports cell membrane integrity, neurotransmitter synthesis, memory, mood regulation and muscle function. The body produces a limited amount, so most choline comes from dietary sources.
Anxiety disorders affect roughly 30% of adults
Richard Maddock, senior author of the study, is a psychiatrist and research professor in the Department of Psychiatry and Behavioral Sciences and a scientist at the UC Davis Imaging Research Center. He and colleagues used advanced MRI-based spectroscopy methods to examine neurometabolite differences linked to anxiety.
“Anxiety disorders are the most common mental illnesses in the United States, affecting about 30% of adults. They can be severely disabling, and many people do not receive adequate treatment,” Maddock noted. The term “anxiety disorders” includes conditions such as generalized anxiety disorder, panic disorder, social anxiety disorder and specific phobias.
How brain systems relate to anxiety
Anxiety disorders reflect altered interactions among brain regions that evaluate threat and control responses. For example, the amygdala signals threat and arousal, while the prefrontal cortex helps regulate responses and supports planning and decision-making. Neurochemical imbalances—such as elevated norepinephrine associated with arousal—also play a role.
In individuals with anxiety disorders, responses to manageable stressors can be exaggerated, producing persistent worry or heightened physiological arousal that interferes with daily life.
Non-invasive spectroscopy measures brain chemistry
Smucny and Maddock have long used proton magnetic resonance spectroscopy (1H-MRS) to measure brain chemicals without invasive procedures. Unlike conventional MRI that images structure, 1H-MRS uses the MRI platform to quantify specific neurometabolites within brain tissue.
Maddock had observed reduced choline in earlier studies of patients with panic disorder and collaborated with Smucny to assess whether this pattern held across anxiety diagnoses. “An 8% reduction may seem modest, but in the brain it represents a meaningful change,” Maddock said.
Dietary choline and public health
The research team hypothesizes that chronic arousal and repeated activation of fight-or-flight pathways could increase the brain’s demand for choline-containing compounds, producing lower measurable tCho when uptake does not keep pace. They emphasize that it remains unknown whether boosting dietary choline will improve anxiety symptoms.
Maddock cautions against self-prescribing high-dose choline supplements. Instead, he recommends that people with anxiety ensure they meet recommended daily choline intake through a balanced diet and consult a clinician before starting supplements. Previous research indicates many people in the U.S., including children, do not reach recommended choline intake levels.
Foods that provide choline include beef liver, eggs (especially yolks), beef, chicken, fish, soybeans and milk. The authors also note that some foods rich in omega-3s, like salmon, may supply nutrients that support brain health and choline-related metabolism.
Key Questions Answered:
A: People with anxiety disorders had approximately 8% lower choline levels in cortical brain regions compared with controls.
A: The deficit was most consistent in the prefrontal cortex, a region involved in cognition, emotion regulation and behavior.
A: Not without medical guidance. More research and clinical trials are needed to determine whether supplementation reduces anxiety symptoms.
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. DOI: 10.1038/s41380-025-03206-7
Abstract
Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis
Background
Anxiety disorders are common, often undertreated, and can be resistant to existing therapies. Although 1H-MRS studies of anxiety disorders have been performed for more than 25 years, there has been no clear consensus about neurometabolic abnormalities across these conditions.
Methods
The authors performed a systematic review and meta-analysis of 1H-MRS studies on social anxiety disorder, generalized anxiety disorder and panic disorder. Twenty-five published datasets met inclusion criteria, together comparing neurometabolite levels—including N-acetylaspartate (NAA), total creatine, total choline (tCho), myo-inositol, glutamate, glutamate+glutamine, GABA and lactate—between 370 patients and 342 controls.
Results
Across anxiety disorders, total choline (tCho) was significantly reduced in the prefrontal cortex and across cortical regions overall. Higher-quality measurement studies showed more negative effect sizes, with Hedges’ g = −0.64 corresponding to an average 8% reduction in cortical tCho. NAA was unchanged in the prefrontal cortex but reduced across all cortical regions after certain exclusions. The observed neurometabolic changes were similar across the three disorders, and no other metabolites differed significantly.
Discussion
A reduction in cortical choline-containing compounds appears to be a consistent, transdiagnostic feature of anxiety disorders. Arousal-related neuromodulators, including norepinephrine, influence membrane phospholipid metabolism and methylation pathways, which can affect brain tCho levels. Chronic elevation of arousal in anxiety disorders could therefore increase demand for choline compounds without a matching increase in brain uptake, producing reduced tCho measurements. Reduced cortical NAA may reflect compromised neuronal function. Future research should clarify the clinical impact of lower cortical tCho and whether appropriately targeted choline interventions could be therapeutically beneficial for anxiety disorders.