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Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis
Anxiety disorders (AnxDs) represent a common yet frequently untreated condition, with ongoing research indicating the need for a comprehensive understanding of their underlying neurometabolic profiles. This systematic review and meta-analysis focuses on proton magnetic resonance spectroscopy (1H-MRS) studies involving social anxiety disorder, generalized anxiety disorder, and panic disorder, encompassing 25 datasets comparing neurometabolite levels between 370 patients and 342 controls.
The findings reveal a significant reduction in total choline (tCho) within the prefrontal cortex and across all cortical regions, with a mean reduction of 8% and an effect size of Hedges’ g = −0.64, particularly pronounced in studies demonstrating superior measurement quality. Conversely, while N-acetylaspartate (NAA) levels remained unchanged in the prefrontal cortex, a reduction was observed across other cortical areas. Notably, these neurometabolic abnormalities did not vary significantly among the three anxiety disorders studied.
The persistent decrease in choline-containing compounds across cortical regions underscores a transdiagnostic neurometabolic abnormality in AnxDs. Elevated arousal-related neuromodulators, such as norepinephrine, may contribute to this phenomenon by disrupting membrane phospholipid homeostasis and methylation processes, thereby increasing the metabolic demand for choline without a corresponding uptick in brain uptake. Additionally, the reduction in cortical NAA suggests potential neuronal dysfunction within these disorders. Future research should aim to elucidate the clinical implications of decreased tCho and explore the therapeutic potential of choline supplementation in mitigating anxiety symptoms.
Year: 2025
