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Controlled Clinical Trial
. 2012 Nov 14;530(1):103-7.
doi: 10.1016/j.neulet.2012.09.054. Epub 2012 Oct 5.

Riluzole effect on occipital cortex: a structural and spectroscopy pilot study

Chadi G Abdallah  1 , Jeremy D Coplan, Andrea Jackowski, João R Sato, Xiangling Mao, Dikoma C Shungu, Sanjay J Mathew
Affiliations
Controlled Clinical Trial

Riluzole effect on occipital cortex: a structural and spectroscopy pilot study

Chadi G Abdallah et al. Neurosci Lett. .

Abstract

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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Conflict of interest statement

Conflict of interest

JDC received grant support from NIMH, NYSTEM, GlaxoSmithKline, Pfizer, and Alexza Pharmaceuticals. He is on the Pfizer advisory board and gives talks for BMS, AstraZeneca, GSK, and Pfizer. SJM: received research funding or salary support over the last three years from the Banner Family Fund, Brain and Behavior Fund (NARSAD), The Brown Foundation, Inc., Bristol-Myers Squibb, Department of Veterans Affairs, Evotec, Johnson & Johnson, and the National Institute of Mental Health. He has received consulting fees or honoraria from Allergan, AstraZeneca, Cephalon, Corcept, Noven, Roche, and Takeda. He has received medication (Rilutek) from Sanofi-Aventis for a NIMH sponsored study. Dr. Mathew has been named as an inventor on a use-patent of ketamine for the treatment of depression. Dr. Mathew has relinquished his claim to any royalties and will not benefit financially if ketamine were approved for this use. No biomedical financial interests or potential conflicts of interest are reported for CGA, AJ, JRS, XM, and DCS.

Figures

Figure 1
Figure 1
In GAD patients, there was a strong negative correlation between right occipital NAA concentration and improvement in HAM-A scores (r = − 0.68, p = 0.008) following 8 weeks of riluzole treatment.
Figure 2
Figure 2
Controlling for age, these statistical maps show clusters of reduced (blue) and increased (red) cortical thickness in the GAD group, as compared to healthy control (z-statistics of each vertex are color coded).
See this image and copyright information in PMC

References

    1. Abdallah CG, Coplan JD, Jackowski A, Sato JR, Mao X, Shungu DC, Mathew SJ. A pilot study of hippocampal volume and N-acetylaspartate (NAA) as response biomarkers in riluzole-treated patients with GAD. Eur Neuropsychopharmacol. 2012 - PMC - PubMed
    1. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000;47:305–313. - PubMed
    1. Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Ashworth F, Sule A, Matthews PM, Cowen PJ. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry. 2007;61:806–812. - PubMed
    1. Binesh N, Kumar A, Hwang S, Mintz J, Thomas MA. Neurochemistry of late-life major depression: a pilot two-dimensional MR spectroscopic study. J Magn Reson Imaging. 2004;20:1039–1045. - PubMed
    1. Block W, Traber F, von Widdern O, Metten M, Schild H, Maier W, Zobel A, Jessen F. Proton MR spectroscopy of the hippocampus at 3 T in patients with unipolar major depressive disorder: correlates and predictors of treatment response. Int J Neuropsychopharmacol. 2009;12:415–422. - PubMed

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