Background: To investigate the mechanism underlying the anxiolytic properties of riluzole, a glutamate-modulating agent, we previously studied the effect of this drug on hippocampal N-acetylaspartate (NAA) and volume in patients with generalized anxiety disorder (GAD). In the same cohort, we now extend our investigation to the occipital cortex, a brain region that was recently implicated in the antidepressant effect of riluzole.
Methods: Fourteen medication-free adult patients with GAD received 8-week of open-label riluzole. Ten healthy subjects served as a comparison group. The healthy group did not receive riluzole treatment. Both groups underwent magnetic resonance imaging and spectroscopy at baseline and at the end of Week 8. Hamilton Anxiety Rating Scale (HAM-A) and Penn State Worry Questionnaire (PSWQ) were used as the primary and secondary outcome measures, respectively.
Results: At baseline, we found clusters of increased cortical thickness in the occipital region in GAD compared to healthy subjects. In the right hemisphere, 8 weeks of treatment reduced occipital cortical thickness in the GAD group (t=3.67, p=0.004). In addition, the improvement in HAM-A scores was negatively correlated with post-treatment right occipital NAA (r=-0.68, p=0.008), and with changes in NAA levels (r=-0.53, p=0.051). In the left hemisphere, we found positive associations between changes in occipital cortical thickness and improvement in HAM-A (r=0.60, p=0.04) and PSWQ (r=0.62, p=0.03).
Conclusion: These pilot findings implicate the occipital cortex as a brain region associated with pathology and clinical improvement in GAD. In addition, the region specific effect of riluzole implies a distinct pathophysiology in the occipital cortex - compared to other, previously studied, frontolimbic brain structures.
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