Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder.
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.
Mathew
Sanjay J
SJ
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA. sanjay.mathew@mssm.edu
Price
Rebecca B
RB
Mao
Xiangling
X
Smith
Eric L P
EL
Coplan
Jeremy D
JD
Charney
Dennis S
DS
Shungu
Dikoma C
DC
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010555:Personality Inventory; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D019782:Riluzole / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D001224:Aspartic Acid; D019782:Riluzole; C000179:N-acetylaspartate