Glutamate level in anterior cingulate predicts anxiety in healthy humans: a magnetic resonance spectroscopy study

Anxiety, a personality dimension in healthy humans, has been found to be associated with many functional consequences such as increased distractibility and attentional bias in favour of threat-related information, along with morphological and microstructural changes in the brain. The associated metabolic/neurochemical alterations are sparsely studied. In the present magnetic resonance spectroscopy (MRS) study, we investigated the possible relationship between regional brain chemistry within anterior cingulate cortex (4-cm(3) voxel) and hippocampus (2.5-cm(3) voxel) and anxiety (measured by State-Trait Anxiety Inventory) in our subject group. In the anterior cingulate cortex, multivariate analysis of covariance showed an increase in myo-inositol and combined glutamate and glutamine levels in the high anxiety subject group as compared with the low anxiety group. In the partial correlation analysis between neurochemicals and anxiety, glutamate and combined glutamate and glutamine also showed a predictive value for anxiety. On analysing the trait anxiety sub-score separately, we found glutamate, inositol and combined glutamate and glutamine levels to be increased in the high trait anxiety group as compared with the low trait anxiety group. All three resonances also had a predictive value for trait anxiety. In the hippocampus, none of the neurochemicals showed significant difference between high and low anxiety groups. The study provides a first account of alterations in anterior cingulate cortex neurochemistry in relation to anxiety in healthy subjects. The study thus contributes to the limited literature available on altered metabolism and neural mechanisms underlying sub-clinical anxiety.