People with anxiety disorders may have a measurable change in brain chemistry involving choline – an essential nutrient associated with memory, mood, cell structure and nerve signaling. Research from UC Davis Health found that people diagnosed with anxiety disorders had lower levels of choline in their brains than people without anxiety disorders. The finding comes from a study published in Molecular Psychiatry, a journal published by Nature, and offers a rare insight into the chemical processes that may be linked to anxiety in various diagnoses.
A Unified Chemical Signal in the Brain
The researchers analyzed data from 25 previous studies in which neurometabolites – the chemicals involved in the brain’s metabolism – were measured. The analysis included a total of 370 people with anxiety disorders and 342 people without anxiety disorders. The most striking result concerned choline. People with anxiety disorders had around 8% lower levels of this nutrient in the brain compared to the control groups. The pattern was particularly evident in the prefrontal cortex, a brain region that helps regulate thoughts, emotions, decision-making 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. “This suggests that nutritional approaches – such as adequate choline supplementation – may help restore brain chemistry and improve treatment outcomes for patients.” Choline plays several important roles in the body. It helps build cell membranes and supports brain functions involved in memory, mood regulation and muscle control. Although the body can produce a small amount itself, the majority of choline must be obtained from the diet.
Why anxiety disorders are important
Anxiety disorders are among the most common mental illnesses worldwide and represent a significant health problem. In the United States, it is estimated that around 30% of adults will be affected by an anxiety disorder in their lifetime. Anxiety disorders are also widespread in Europe: It is estimated that around one in seven adults suffers from some form of anxiety disorder every year. These disorders not only affect emotional well-being, but often also impact work, relationships, physical health and overall quality of life.
Psychiatrist and neuroscientist Richard Maddock has been studying how anxiety disorders affect the brain for many years. As a research professor at the UC Davis Imaging Research Center, he uses magnetic resonance imaging (MRI) to study the changes that occur in the brain of people with anxiety disorders. The goal of this research is to better understand why anxiety becomes chronic in some people and how more effective treatments can be developed. Maddock emphasizes that anxiety disorders are often underestimated, even though such anxiety can be extremely distressing for sufferers. Those affected often avoid certain situations or social contacts, which can lead to long-term isolation and restrictions in everyday life. The most important forms of anxiety disorders include
- generalized anxiety disorder, which is characterized by persistent worries that are difficult to control,
- panic disorder, which is characterized by sudden, intense attacks of anxiety,
- social anxiety disorder, in which sufferers have a great fear of being judged or rejected by other people,
- and specific phobias, i.e. strong fears of certain objects or situations, such as heights, spiders or confined spaces.
A key problem is that many sufferers do not receive appropriate treatment. Reasons for this include feelings of shame, a lack of information or a lack of access to psychotherapeutic help.
How the Brain Processes Anxiety and Stress
Anxiety disorders are linked to the way the brain responds to stress, danger and uncertainty. Two key regions are often involved: the amygdala, which helps determine feelings of safety or threat, and the prefrontal cortex, which supports planning, decision-making and emotional control. When this system is functioning well, the brain can usually distinguish manageable problems from serious threats. With anxiety disorders, this balance can shift. Everyday worries can feel overwhelming, and the body’s stress response can be difficult to calm.
Brain chemistry also plays a role. Anxiety disorders have been linked to changes in neurotransmitters, including norepinephrine, which is part of the body’s “fight-or-flight” response. Norepinephrine is often elevated in anxiety disorders, and the UC Davis researchers hypothesize that this increased arousal may increase the brain’s need for choline. In generalized anxiety disorder, for example, sufferers worry excessively and persistently about everyday events or potential future problems. The fears often concern areas such as work, health, family, finances or interpersonal relationships and are often disproportionate to the actual situation.
Many sufferers find it difficult to control their worries or switch off mentally, even if they know that their fears seem exaggerated. In addition to the constant inner tension, physical complaints often occur, including sleep disorders, muscle tension, concentration problems, rapid exhaustion, palpitations or inner restlessness. The constant stress can have a considerable impact on everyday life and mean that those affected can hardly relax or constantly anticipate possible negative events. Generalized anxiety disorders often develop gradually and can persist for many years without treatment.
Measuring Brain Chemicals Without Surgery
For many years, Richard Maddock and Jeremiah Smucny have been using proton magnetic resonance spectroscopy (1H-MRS) to investigate how changes in brain chemistry are linked to mental illness. This method is considered particularly valuable because it is non-invasive and does not require surgical intervention. The examination is carried out with an MRI machine, but not only uses classic imaging of the brain structure, but also measures the concentration of certain chemical substances in the brain tissue using magnetic fields and radio waves.
This allows researchers to obtain information on how nerve cells work, how active certain metabolic processes are and whether changes in brain chemistry are associated with mental illness. Substances such as choline and N-acetylaspartate (NAA) are of particular interest. NAA is often regarded as a marker for the health, functionality and density of nerve cells. Reduced NAA levels can indicate changes in neuronal function or stress levels in the brain.
In earlier studies, Maddock had already found lower choline levels in people with panic disorder. Together with Smucny, these results ultimately led to a larger meta-analysis in which numerous earlier studies were evaluated. Although the researchers had already expected changes in choline levels, what was particularly striking was how consistent the results were across different anxiety disorders. The concentration of choline-containing compounds was reduced by around eight percent on average – a value that is considered significant and biologically relevant in the sensitive chemical balance of the brain. The results suggest that anxiety disorders may not only be associated with psychological stress, but also have measurable changes in brain chemistry. In particular, the reduced amount of choline-containing compounds could indicate that processes of cell communication, energy metabolism or the stability of nerve cell membranes are impaired.
Choline, nutrition and mental health
Researchers suspect that chronic “fight-or-flight” responses may increase the brain’s need for choline. If the brain can’t absorb enough choline to meet these needs, choline levels could drop. However, this does not mean that choline supplements are a proven treatment for anxiety. Maddock emphasized that this question remains open.
“We don’t yet know if increasing dietary choline intake helps reduce anxiety. More research is needed,” Maddock said. He cautions that people with anxiety disorders should not self-medicate with excessive choline supplements. Still, this finding adds to the growing interest in the link between nutrition and mental health. It is already known that choline is important for the brain and nervous system, and many people in the United States do not consume the recommended daily amount. “Someone with an anxiety disorder may want to review their diet and see if they are consuming the recommended daily amount of choline. Previous research has shown that most people in the U.S., including children, are not getting the recommended daily amount,” Maddock said. Certain forms of omega-3 fatty acids, such as those found in salmon, may be particularly good sources of choline for the brain.
Since the publication of the UC Davis study, the overall picture of the research remains intriguing, but not yet settled. Related dietary studies in adults suggest that higher choline intake may be associated with a lower risk of depression, but the same study found no significant adjusted association with anxiety or psychological distress.
This makes the UC Davis brain imaging results particularly interesting. They suggest a measurable chemical difference in the brain, but do not prove that a low choline diet causes anxiety or that increasing choline intake relieves symptoms. Controlled studies would be needed to test whether altering choline intake can affect brain chemistry or improve anxiety symptoms. For now, the results support a practical but cautious message: diet may be one piece of the anxiety puzzle, but it is no substitute for professional psychological care.
Foods that provide this important nutrient
Beef liver, eggs – especially the yolk – beef and chicken, fish, soybeans, milk and dairy products are particularly rich in choline. Plant-based foods such as pulses, broccoli and nuts also provide choline, although usually in smaller quantities. In addition to many other functions, choline plays an important role in the regulation of inflammatory processes and in protecting cells from damage. Scientific studies suggest that an adequate intake of choline may be linked to better cardiovascular health and a healthy metabolism. As choline is also involved in the processing of homocysteine – an amino acid whose elevated levels are associated with cardiovascular disease – the nutrient is considered an important part of a balanced diet.
A lack of choline over a long period of time can lead to liver problems, muscle weakness or concentration problems, among other things. An adequate supply is particularly important during pregnancy and breastfeeding. Choline supports the development of the unborn child’s brain and nervous system and could have a long-term effect on memory and learning abilities. Experts therefore recommend that expectant mothers make sure their diet is rich in choline.
The study highlights a possible biological link between anxiety and a nutrient that the brain relies on daily. It also raises a larger question for future research: whether improving choline status could help restore brain chemistry in people with anxiety disorders. For now, researchers say the answer is not yet known. But the discovery gives scientists a clearer chemical target for their investigations and offers people another reason to pay attention to those nutrients that support brain health.