Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder.

TitleHippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder.
Publication TypeJournal Article
Year of Publication2008
AuthorsMathew SJ, Price RB, Mao X, Smith ELP, Coplan JD, Charney DS, Shungu DC
JournalBiol Psychiatry
Volume63
Issue9
Pagination891-8
Date Published2008 May 01
ISSN1873-2402
KeywordsAdult, Anti-Anxiety Agents, Anxiety Disorders, Aspartic Acid, Excitatory Amino Acid Antagonists, Female, Gyrus Cinguli, Hippocampus, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Personality Inventory, Prefrontal Cortex, Riluzole, Treatment Outcome
Abstract

BACKGROUND: Previous research has suggested the therapeutic potential of glutamate-modulating agents for severe mood and anxiety disorders, potentially resulting from enhancement of neuroplasticity. We used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to examine the acute and chronic effects of the glutamate-release inhibitor riluzole on hippocampal N-acetylaspartate (NAA), a neuronal marker, in patients with generalized anxiety disorder (GAD) and examined the relationship between changes in NAA and clinical outcome.

METHODS: Fourteen medication-free GAD patients were administered open-label riluzole and then evaluated by (1)H MRSI before drug administration, and 24 hours and 8 weeks following treatment. Patients were identified as responders (n = 9) or nonresponders (n = 5). Seven untreated, medically healthy volunteers, comparable in age, sex, IQ, and body mass index to the patients, received scans at the same time intervals. Molar NAA concentrations in bilateral hippocampus, and change in anxiety ratings were the primary outcome measures.

RESULTS: A group-by-time interaction was found, with riluzole responders showing mean increases in hippocampal NAA across the three time points, whereas nonresponders had decreases over time. In GAD patients at Week 8, hippocampal NAA concentration and proportional increase in NAA from baseline both were positively associated with improvements in worry and clinician-rated anxiety.

CONCLUSIONS: These preliminary data support a specific association between hippocampal NAA and symptom alleviation following riluzole treatment in GAD. Placebo-controlled investigations that examine hippocampal NAA as a viable surrogate endpoint for clinical trials of neuroprotective and plasticity-enhancing agents are warranted.

DOI10.1016/j.biopsych.2007.09.012
Alternate JournalBiol Psychiatry
PubMed ID18028881
PubMed Central IDPMC2385784
Grant ListK23 MH069656 / MH / NIMH NIH HHS / United States
K23 MH069656-02 / MH / NIMH NIH HHS / United States
K23-MH-069656 / MH / NIMH NIH HHS / United States
Related Institute: 
MRI Research Institute (MRIRI)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065