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Functional MRI (fMRI) to monitor psychosis

Mouse and human studies suggest fMRI could be useful for detecting the onset of psychosis. In patients with a history of psychosis, fMRI at the onset of psychotic episodes showed decreased hippocampus size but increased hippocampal activity compared with that of nonpsychotic controls. In an fMRI study of mice with acute ketamine-induced psychosis, imaging showed that LY379286, a metabotropic glutamate receptor subtype 2 (mGluR2; GRM2) and mGluR3 (GRM3) agonist, decreased hippocampal atrophy and hyperactivity compared with vehicle. Next steps include scaling up clinical imaging studies to identify at-risk patients and testing the effect of mGluR2 and/or mGluR3 modulators on hippocampal activity.
Eli Lilly and Co.'s Pomaglumetad methionil, an oral prodrug of an mGlur2 and mGluR3 agonist, was discontinued last year after missing the endpoints in a Phase III trial to treat schizophrenia.
Roche, Addex Therapeutics Ltd. and Taisho Pharmaceutical Holdings Co. Ltd. have compounds in this class in Phase I and II testing to treat various neuropsychiatric indications.

SciBX 6(17); doi:10.1038/scibx.2013.427
Published online May 2, 2013

Unpatented; licensing status not applicable

Schobel, S.A. et al. Neuron;
published online April 10, 2013;
Contact: Scott A. Small, Columbia University Medical Center, New York, N.Y.
Contact: Holly Moore, same affiliation as above