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

Publication ,  Journal Article
Jarskog, LF; Dong, Z; Kangarlu, A; Colibazzi, T; Girgis, RR; Kegeles, LS; Barch, DM; Buchanan, RW; Csernansky, JG; Goff, DC; Harms, MP ...
Published in: Neuropsychopharmacology
June 2013

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.

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Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

June 2013

Volume

38

Issue

7

Start / End Page

1245 / 1252

Location

England

Related Subject Headings

  • Schizophrenic Psychology
  • Schizophrenia
  • Psychiatry
  • Prefrontal Cortex
  • Oligopeptides
  • Middle Aged
  • Male
  • Humans
  • Functional Neuroimaging
  • Female
 

Citation

APA
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ICMJE
MLA
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Jarskog, L. F., Dong, Z., Kangarlu, A., Colibazzi, T., Girgis, R. R., Kegeles, L. S., … Lieberman, J. A. (2013). Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia. Neuropsychopharmacology, 38(7), 1245–1252. https://doi.org/10.1038/npp.2013.23
Jarskog, L Fredrik, Zhengchao Dong, Alayar Kangarlu, Tiziano Colibazzi, Ragy R. Girgis, Lawrence S. Kegeles, Deanna M. Barch, et al. “Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia.Neuropsychopharmacology 38, no. 7 (June 2013): 1245–52. https://doi.org/10.1038/npp.2013.23.
Jarskog LF, Dong Z, Kangarlu A, Colibazzi T, Girgis RR, Kegeles LS, et al. Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia. Neuropsychopharmacology. 2013 Jun;38(7):1245–52.
Jarskog, L. Fredrik, et al. “Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia.Neuropsychopharmacology, vol. 38, no. 7, June 2013, pp. 1245–52. Pubmed, doi:10.1038/npp.2013.23.
Jarskog LF, Dong Z, Kangarlu A, Colibazzi T, Girgis RR, Kegeles LS, Barch DM, Buchanan RW, Csernansky JG, Goff DC, Harms MP, Javitt DC, Keefe RS, McEvoy JP, McMahon RP, Marder SR, Peterson BS, Lieberman JA. Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia. Neuropsychopharmacology. 2013 Jun;38(7):1245–1252.

Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

June 2013

Volume

38

Issue

7

Start / End Page

1245 / 1252

Location

England

Related Subject Headings

  • Schizophrenic Psychology
  • Schizophrenia
  • Psychiatry
  • Prefrontal Cortex
  • Oligopeptides
  • Middle Aged
  • Male
  • Humans
  • Functional Neuroimaging
  • Female