Anxiety in healthy humans is associated with orbital frontal chemistry

The present study examines relationships between regional brain chemistry (as identified by localized in vivo three-dimensional single-voxel proton magnetic resonance spectroscopy (1H-MRS) and anxiety (as measured by the State-Trait Anxiety Inventory) in 16 healthy subjects. The relative concentrations of N-Acetyl aspartate, choline, glutamate, glutamine, gamma-aminobutyric acid, inositol, glucose and lactate were measured relative to creatine within six 8-cm3 brain voxels localized to: thalamus, cingulate, insula, sensorimotor, dorsolateral prefrontal, and orbital frontal cortices (OFC) in the left hemisphere. Analysis of variance, across brain regions, chemicals, and high and low anxiety groups, showed a relationship between anxiety and chemical composition of OFC, with high anxiety subjects demonstrating 32% increase in overall chemical concentrations within OFC, as compared to the lower anxiety group (F= 60.8, P < 10(-7)). Other brain regions, including cingulate, showed no detectable anxiety dependence. The combination of the state and trait anxiety was highly correlated with the concentration of OFC chemicals (r2 = 0.98), and N-Acetyl aspartate in OFC was identified as the strongest chemical marker for anxiety (changed by 43.2% between the two anxiety groups, F = 21.5, P = 0.000005). The results provide direct evidence that the OFC chemistry is associated with anxiety in healthy humans. The method can be used as a neuroimaging/behavioral tool for documentation of OFC chemistry changes in relation to anxiety per se and anxiety disorders. The presented relationship between regional brain chemistry and anxiety reflects the functional/behavioral state of the brain, pointing to possible mechanisms of the neurobiology of anxiety.