John G Csernansky Feinberg School of Medicine, Feinberg Clinical, Psychiatry and Behavioral Sciences

John G Csernansky

Research Interest Keywords

Clinical Trial Methodology, Cognitive Neuroscience, Dementia, Interdisciplinary Research, Neuroscience, Psychiatry, Psychosis, Quantitative MRI, Schizophrenia

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Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia

L. Fredrik Jarskog; Zhengchao Dong; Alayar Kangarlu; Tiziano Colibazzi; Ragy R Girgis; Lawrence S. Kegeles; Deanna M. Barch; Robert W. Buchanan; John G. Csernansky; Donald C. Goff; et al.

(Profiled Author: John G Csernansky)

Neuropsychopharmacology. 2013;38(7):1245-1252.

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. © 2013 American College of Neuropsychopharmacology.


PMID: 23325325     PMCID: PMC3656368    

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