Most people assume anxiety is a neurotransmitter problem – a result of too little serotonin, or not enough GABA, the brain’s main calming chemical.
Some presume it is just an imbalance a prescription might correct. Remedying these things are what medications are created to target, and how chemical pathways are informed.
However, something called choline didn’t make that list and is not usually considered in treating anxiety.
It’s a dietary nutrient found in eggs and beef liver and is often utilized for its positive effect on liver health.
However, a sweeping review of two decades of brain chemistry data is showing something unexpected – choline may also improve mood.
Studying choline and anxiety
The reading comes from proton magnetic resonance spectroscopy, an MRI technique that does not produce images.
Instead, it measures the concentrations of small molecules that gather inside brain tissue.
Researchers have used the technique on people with anxiety disorders for more than 25 years. The literature, until recently, was a mess of inconsistent results.
Dr. Richard J. Maddock at the University of California, Davis (UC Davis) set out with his colleague Dr. Jason Smucny to comb through that literature and look for a signal.
They pulled together 25 datasets from 24 published studies, covering 370 people with an anxiety disorder and 342 controls without one.
One molecule kept dropping hints. Choline-containing compounds in the cortex were about eight percent lower in patients than in the controls.
An eight percent gap
In the broader cortex, the gap between patients and controls held up even when only the highest-quality scans were included.
This showed a surprising and consistent difference by the standards of brain chemistry research.
While the eight percent average reduction sounds modest in everyday terms, it cannot be ignored.
“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” said Maddock.
Answers from within
The clearest signal showed up in the prefrontal cortex. This region, situated behind the forehead, handles planning, judgment, and the rational override of fear.
This provided six datasets, all in the same region, and all headed in the same direction.
What this looks like on the scan is not overly dramatic. The spectroscopy returns a curve with peaks at different frequencies.
Meanwhile, the choline peak rises a little lower in the patient group than in controls.
When that is repeated across hundreds of patients, the difference holds and remains.
The technique is sensitive enough to catch a chemistry change in cortical tissue that conventional brain imaging would miss completely.
Three differing disorders
The reduction did not depend on which anxiety diagnosis a patient had. People with generalized anxiety disorder, panic disorder, and social anxiety disorder all showed the same dip in the data.
Each of the patients showed a pattern going in the same direction, in the same region, with roughly the same magnitude.
That cross-cutting consistency is the part Maddock did not expect. His earlier research had already turned up abnormal brain chemistry in patients with panic disorder.
Until this meta-analysis, no one had clearly demonstrated the pattern across all three of the most common anxiety conditions.
That cross-disorder consistency is new, and it is the first time it’s been established in the literature.
A theory of why
Maddock and Smucny think the dip might track back to chronically elevated arousal.
Anxiety keeps the brain’s alerting system running at a higher pitch than normal. That constant activity may increase demand for choline faster than the brain can replenish it.
Demand goes up and supply, presumably, does not keep up the same pace.
Whether anxiety depletes choline through metabolic burn or simply outstrips what diet and internal production can deliver, the team cannot say from imaging alone.
The source of choline
Choline is an essential nutrient. The body makes some of it, but most has to come from food.
Eggs are the densest common source, especially the yolk. It is also contained in beef liver, salmon, chicken, soybeans, and milk.
Federal guidance puts the daily amount at 550 milligrams for men and 425 milligrams for most women. Surveys suggest about nine in ten American adults fall short of those targets.
Be wary of supplements
It is important to note that the review does not prove that low choline causes anxiety. It does not prove that choline pills relieve it, either. Large doses can carry side effects.
Anxiety needs evaluation and treatment from clinicians. The contours of diet, however, may be worth a conversation.
Someone with an anxiety disorder who is already short on choline at the dinner table has at least one variable worth checking.
Choline, anxiety, and treatment
Anxiety now has a brain chemistry marker that the field can depend on. Lower cortical choline is present in all three disorder types.
This data can further sharpen future studies, research that is anchored in the prefrontal cortex. This reality was not established a year ago.
There are practical questions to follow that must be answered. For example, brain scans may eventually be able to confirm an anxiety diagnosis or distinguish it from related conditions.
There is also room for nutrition counseling to pays attention to choline, especially for deficient patients.
And eventually, a targeted trial of dietary support in unmedicated patients could finally test the causal direction.
None of those answers exist yet. The chemistry, however, does, and has better language for future treatment options.
The study is published in Molecular Psychiatry.
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