Article

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

Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Biological psychiatry (Impact Factor: 9.47). 06/2008; 63(9):891-8. DOI: 10.1016/j.biopsych.2007.09.012
Source: PubMed

ABSTRACT 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.
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.
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.
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.

Full-text

Available from: Dikoma C Shungu, May 05, 2015
0 Followers
 · 
108 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS). We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables. Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA. Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
    01/2014; 4:326-35. DOI:10.1016/j.nicl.2013.12.014
  • Brain Behavior and Immunity 08/2011; 25. DOI:10.1016/j.bbi.2011.07.126 · 6.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to review data for several promising novel pharmacological drugs for anxiety disorders and describe how they exert their effects. We presented a review of the published literature. Online search plus reference list checking was also used. The neurobiology of anxiety is overviewed. N-methyl-D-aspartate and beta adrenaline are involved in memory consolidation. We describe studies using memantine, D-cycloserine, propranolol, and riluzole that modulate these pathways. There are a number of promising new therapies, but these require further studies before they can enter routine clinical practice. Copyright © 2013 John Wiley & Sons, Ltd.
    Human Psychopharmacology Clinical and Experimental 11/2013; 28(6). DOI:10.1002/hup.2348 · 1.85 Impact Factor