Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia.

Abstract

AIM:

We have previously found that sarcosine, a glycine transporter I inhibitor, can improve the psychiatric symptoms of schizophrenia. In this study, we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson's disease (PD) patients with dementia.

METHODS:

An 8-week, double-blind, placebo-controlled trial was conducted in patients who had PD with dementia (PD-D). Neuropsychiatric manifestations were measured before and at week 2 (V1), week 4 (V2) and week 8 (V3) after treatment. Linear regression with the generalized estimating equations was applied for data analysis.

RESULTS:

Fifteen patients were randomized into a sarcosine group; the other 15 into a placebo group. The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score (P = 0.049) at V1 and Neuropsychiatry Inventory (P = 0.039) at V2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in Unified Parkinson's Disease Rating Scale V2 (P = 0.004) and V3 (P = 0.040), Hamilton Depression Rating Scale V1 (P = 0.014) and V2 (P = 0.047), Neuropsychiatry Inventory V1 (P = 0.002) and V2 (P < 0.001) and Behavior Pathology in Alzheimer's Disease Rating Scale V2 (P = 0.025) in favor of sarcosine.

CONCLUSION:

Sarcosine temporally improved depression and neuropsychiatric symptoms in PD-D patients without exacerbating the motor or cognitive features; the beneficial effects were more prominent in patients with mild-moderate severity. Enhancement of N-methyl-D-aspartate receptor-glycine cascade may lead to a novel path for the management of PD-D.

• Authors: Chon-Haw Tsai, Hui-Chun Huang, Bey-Ling Liu, Chia-Ing Li, Ming-Kuei Lu, Xianxiu Chen, Mu-Chieh Tsai, Yu-Wan Yang, Hsien-Yuan Lane
• Journal: Psychiatry and clinical neurosciences (Psychiatry Clin Neurosci) Vol. 68 Issue 9 Pg. 692-700 (Sep 2014) ISSN: 1440-1819 [Electronic] Australia
• PMID: 24612097 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Chemical References

• Receptors, N-Methyl-D-Aspartate
• Sarcosine

Topics

• Aged
• Aged, 80 and over
• Dementia (complications, drug therapy)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Parkinson Disease (complications, drug therapy)
• Receptors, N-Methyl-D-Aspartate (agonists)
• Sarcosine (therapeutic use)
• Treatment Outcome