Cited by 168Bipolar Disorder and TreatmentTreatment of Major DepressionSchizophrenia research and treatment

Rapid Enhancement of Glutamatergic Neurotransmission in Bipolar Depression Following Treatment with Riluzole

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Brennan, Brian P, Hudson, James I, Jensen, J Eric, McCarthy, Julie, Roberts, Jacqueline L, Prescot, Andrew P, Cohen, Bruce M, Pope, Harrison G +2 more·2010·Neuropsychopharmacology

Abstract

Glutamatergic abnormalities may underlie bipolar disorder (BD). The glutamate-modulating drug riluzole may be efficacious in bipolar depression, but few in vivo studies have examined its effect on glutamatergic neurotransmission. We conducted an exploratory study of the effect of riluzole on brain glutamine/glutamate (Gln/Glu) ratios and levels of N-acetylaspartate (NAA). We administered open-label riluzole 100-200 mg daily for 6 weeks to 14 patients with bipolar depression and obtained imaging data from 8-cm(3) voxels in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) at baseline, day 2, and week 6 of treatment, using two-dimensional J-resolved proton magnetic resonance spectroscopy at 4 T. Imaging data were analyzed using the spectral-fitting package, LCModel; statistical analysis used random effects mixed models. Riluzole significantly reduced Hamilton Depression Rating Scale (HAM-D) scores (d=3.4; p<0.001). Gln/Glu ratios increased significantly by day 2 of riluzole treatment (Cohen's d=1.2; p=0.023). NAA levels increased significantly from baseline to week 6 (d=1.2; p=0.035). Reduction in HAM-D scores was positively associated with increases in NAA from baseline to week 6 in the ACC (d=1.4; p=0.053), but was negatively associated in the POC (d=9.6; p<0.001). Riluzole seems to rapidly increase Gln/Glu ratios-suggesting increased glutamate-glutamine cycling, which may subsequently enhance neuronal plasticity and reduce depressive symptoms. Further investigation of the Gln/Glu ratio as a possible early biomarker of response to glutamate-modulating therapies is warranted.

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  • Riluzole increases glutamate-glutamine cycling, a potential explanation for in vitro observations of enhanced neuroplasticity and amelioration of excitotoxicity, as well as in vivo reductions in depressive behaviors.

    “Riluzole also increases glutamate–glutamine cycling, a potential explanation for in vitro observations of enhanced neuroplasticity and amelioration of excitotoxicity [176,177], as well as in vivo reductions in depressive behaviors [144,178].”

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Authors
Brennan, B. P., Hudson, J. I., Jensen, J. E., McCarthy, J., Roberts, J. L., Prescot, A. P., Cohen, B. M., Pope, H. G., Renshaw, P. F., & Öngür, D.
Affiliations
  • McLean Hospital (US)
  • Harvard University (US)
  • University of Utah (US)
Corresponding author
Brennan, Brian P
Venue
Neuropsychopharmacology
Published
2009-12-02
Volume
35
Issue
3
Pages
834-846
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W2019754485
Cited by
168
References
68
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 27 · 2020: 4 · 2019: 9 · 2018: 4 · 2017: 10 · 2016: 11 · 2015: 17 · 2014: 12 · 2013: 14 · 2012: 12
FWCI
7.42
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company
  • Pfizer
  • GlaxoSmithKline
  • Sanofi
  • National Alliance for Research on Schizophrenia and Depression
  • Janssen Scientific Affairs
  • National Institute of Mental Health (R01MH058618, K23MH079982)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
riluzole, bipolar depression, glutamatergic neurotransmission, glutamine/glutamate ratio, N-acetylaspartate, anterior cingulate cortex, parieto-occipital cortex, 1H NMR, treatment response biomarkers
MeSH terms
Adult, Bipolar Disorder, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Synaptic Transmission, Psychiatric Status Rating Scales, Time Factors, Treatment Outcome, Glutamic Acid, Riluzole, Young Adult

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