Anxiety disorders share a brain signature of reduced cortical choline levels. Digest
Anxiety disorders are common and often difficult to treat, yet we still lack a clear understanding of the brain's chemical and metabolic changes that could guide new therapies. In a new meta-analysis, researchers examined which brain metabolites differ between patients with social anxiety disorder, generalized anxiety disorder, or panic disorder and healthy volunteers.
The study included 25 human datasets covering 370 patients and 342 healthy controls, all scanned with proton magnetic resonance spectroscopy, an imaging technique that can measure brain metabolites. The investigators focused on eight commonly reported metabolite measures: total choline-containing compounds, N-acetylaspartate (NAA), total creatine, myo-inositol, glutamate, glutamate plus glutamine, gamma-aminobutyric acid (GABA), and lactate.
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The analysis revealed a characteristic pattern of brain chemistry in anxiety disorders compared with controls:
- Choline levels were consistently lower in the brain's outer regions (the cortex) in people with anxiety disorders. Across studies, this reduction averaged about 8%, making it the strongest and most reliable finding.
- NAA levels were also lower, but this pattern was weaker and less consistent than the choline result.
- In unmedicated patients, creatine also appeared lower, but this result is uncertain due to suboptimal measurement methods.
- Deeper brain regions (subcortical areas) such as the basal ganglia and hippocampus did not show clear differences in choline or NAA.
- The other measured brain chemicals did not show reliable differences between people with anxiety and healthy volunteers.
- The size of the choline reduction was similar in generalized anxiety disorder, panic disorder, and social anxiety disorder, pointing to a shared pattern across these diagnoses.
The brain depends heavily on choline, and its supply can drop when demand outpaces uptake from the bloodstream. Anxiety disorders are marked by persistent overactivation of arousal-related systems, including the noradrenergic stress network. This kind of long-term arousal may increase the brain's need for choline, for example to support myelination, the process of building and maintaining the myelin sheath that insulates nerve fibers and helps them transmit signals efficiently.
The pattern for NAA fits into this broader picture. In other psychiatric conditions, larger drops in NAA tend to appear together with actual thinning of cortical tissue. This combination has not been observed in anxiety disorders, but the small and inconsistent NAA reduction seen in this analysis may point to a subtle metabolic strain on neurons.
The study is limited by the modest number of datasets, incomplete reporting on measurement quality, and its correlational design, which cannot establish causality. Even so, it highlights reduced cortical choline as a consistent pattern across anxiety disorders and an interesting target for future mechanistic and supplementation trials. In Aliquot #67, I talk about the role of choline in metabolic and brain health.