Back to Search Start Over

Effects of Davunetide on N-acetylaspartate and Choline in Dorsolateral Prefrontal Cortex in Patients with Schizophrenia

Authors :
Tiziano Colibazzi
John G. Csernansky
Ragy R. Girgis
Lawrence S. Kegeles
Robert W. Buchanan
Bradley S. Peterson
Alayar Kangarlu
Jeffrey A. Lieberman
Zhengchao Dong
L. Fredrik Jarskog
Richard S.E. Keefe
Joseph P. McEvoy
Michael P. Harms
M Deanna
Donald C. Goff
Stephen R. Marder
Robert P. McMahon
Daniel C. Javitt
Source :
Neuropsychopharmacology. 38:1245-1252
Publication Year :
2013
Publisher :
Springer Science and Business Media LLC, 2013.

Abstract

Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in animal models of neurodegeneration. Davunetide has recently demonstrated modest functional improvement in a study of people with schizophrenia. In a subset of these subjects, proton magnetic resonance spectroscopy ((1)H-MRS) was conducted to explore the effects of davunetide on change in NAA/creatine (NAA/Cr) and choline/creatine (choline/Cr) over 12 weeks of treatment. Of 63 outpatients with schizophrenia who received randomized davunetide (5 and 30 mg/day) or placebo in the parent clinical trial, 18 successfully completed (1)H-MRS in dorsolateral prefrontal cortex (DLPFC) at baseline and at 12 weeks. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB). NAA/Cr was unchanged for combined high- and low-dose davunetide groups (N=11). NAA/Cr in the high-dose davunetide group (N=8) suggested a trend increase of 8.0% (P=0.072) over placebo (N=7). Choline/Cr for combined high- and low-dose davunetide groups suggested a 6.4% increase (P=0.069), while the high-dose group showed a 7.9% increase (P=0.040) over placebo. Baseline NAA/Cr correlated with the composite MCCB score (R=0.52, P=0.033), as did individual cognitive domains of attention/vigilance, verbal learning, and social cognition; however, neither metabolite correlated with functional capacity. In this exploratory study, 12 weeks of adjunctive davunetide appeared to produce modest increases in NAA/Cr and choline/Cr in DLPFC in people with schizophrenia. This is consistent with a potential neuroprotective mechanism for davunetide. The data also support use of MRS as a useful biomarker of baseline cognitive function in schizophrenia. Future clinical and preclinical studies are needed to fully define the mechanism of action and cognitive effects of davunetide in schizophrenia.

Details

ISSN :
1740634X and 0893133X
Volume :
38
Database :
OpenAIRE
Journal :
Neuropsychopharmacology
Accession number :
edsair.doi.dedup.....2e9013da20f863982a43a20029ee2e10
Full Text :
https://doi.org/10.1038/npp.2013.23